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Inflammation
Journal Prestige (SJR): 1.023  Citation Impact (citeScore): 3 Number of Followers: 3  Hybrid journal (It can contain Open Access articles)ISSN (Print) 1573-2576 - ISSN (Online) 0360-3997 Published by Springer-Verlag  [2469 journals]
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- JNK/Itch Axis Mediates the Lipopolysaccharide-Induced
Ubiquitin–Proteasome–Dependent Degradation of Ferritin Light Chain in
Murine Macrophage Cells-
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Abstract: Abstract Ferritin, which is composed of a heavy chain and a light chain, plays a critical role in maintaining iron homeostasis by sequestering iron. The ferritin light chain (FTL) is responsible for the stability of the ferritin complex. We have previously shown that overexpression of FTL decreases the levels of the labile iron pool (LIP) and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-treated murine macrophage cells. The protein level of FTL was downregulated by LPS within a short treatment period. However, the mechanism underlying the LPS-induced changes in the FTL levels is not known. In the present study, we report that LPS induces the ubiquitin–proteasome-dependent degradation of FTL and that the mechanism of LPS-induced FTL degradation involves the JNK/Itch axis. We found that LPS downregulates the protein and mRNA levels of FTL in a time-dependent manner. The proteasome inhibitor MG-132 significantly reverses the LPS-induced decrease in FTL. Furthermore, we observed that LPS treatment cannot cause ubiquitination of the lysine site (K105 and K144) mutant of FTL. Interestingly, LPS-mediated ubiquitin-dependent degradation of FTL is significantly inhibited by the JNK-specific inhibitor SP600125. Moreover, LPS could upregulate the protein level of E3 ubiquitin ligase Itch, a substrate of JNK kinases. Immunoprecipitation analyses revealed an increase in the association of FTL with Itch, a substrate of JNK kinases, in response to LPS stimulation. SP600125 decreased LPS-induced Itch upregulation. Taken together, these results suggest that LPS stimulation leads to the degradation of FTL through the ubiquitin–proteasome proteolytic pathway, and this FTL degradation is mediated by the JNK/Itch axis in murine macrophage cells.
PubDate: 2022-06-01
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- Expression Pattern and Immunoregulatory Roles of Galectin-1 and Galectin-3
in Atopic Dermatitis and Psoriasis-
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Abstract: The pathogenesis of atopic dermatitis (AD) and psoriasis (Ps) overlaps, particularly the activation of the immune response and tissue damage. Here, we evaluated galectin (Gal)-1 and Gal-3 levels, which are beta-galactoside-binding proteins with immunomodulatory functions and examined their effects on human keratinocytes stimulated with either interleukin (IL)-4 or IL-17A. Skin biopsies from AD, Ps, and control patients were evaluated using histological and immunohistochemical analyses. Six studies containing publicly available transcriptome data were individually analyzed using the GEO2R tool to detect Gal-1 and Gal-3 mRNA levels. In vitro, IL-4- or IL-17A-stimulated keratinocytes were treated with or without Gal-1 or Gal-3 to evaluate cytokine release and migration. Our findings showed different patterns of expression for Gal-1 and Gal-3 in AD and Ps skins. Densitometric analysis in skin samples showed a marked increase in the protein Gal-1 levels in Ps epidermis and in both AD and Ps dermis compared to controls. Protein and mRNA Gal-3 levels were downregulated in AD and Ps lesional skin compared with the control samples. In vitro, both galectins addition abrogated the release of IL-8 and RANTES in IL-17-stimulated keratinocytes after 24 h, whereas IL-6 release was downregulated by Gal-3 and Gal-1 in IL-4- and IL-17-stimulated cells, respectively. Administration of both galectins also increased the rate of keratinocyte migration under IL-4 or IL-17 stimulation conditions compared with untreated cells. Altogether, the immunoregulatory and migration effects of Gal-1 and Gal-3 on keratinocytes under inflammatory microenvironment make them interesting targets for future therapies in cutaneous diseases. Graphical abstract
PubDate: 2022-06-01
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- LncRNA HCP5 Participates in the Tregs Functions in Allergic Rhinitis and
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Abstract: Abstract Allergic rhinitis (AR) is an allergic disease characterized as (immunoglobulin, IgE)-mediated type I hypersensitivity disorder. Regulatory T cells (Tregs) play a crucial role in AR. In the present study, we aimed to investigate the mechanism of how Tregs are regulated by long noncoding RNA HCP5 and the regulatory role of HCP5 in IL-13-induced inflammatory response in nasal epithelial cells (NECs) from AR patients. Peripheral blood mononuclear cells (PBMCs) and NECs were obtained from collected blood samples and nasal epithelial tissues. CD4+ T cells and Tregs were purified using certain cell isolation kits from PBMCs and Tregs were also differentiated from CD4+ T cells using recombinant human IL-2 and TGF-β. The expression levels of HCP5, miR-16, ATXN2L, GM-CSF, eotaxin, and MUC5AC were detected by real-time PCR and western blot. The concentrations of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The interaction among HCP5, miR-16, and ATXN2L were verified by dual-luciferase reporter assay. lncRNA HCP5 expression dramatically downregulated in PBMCs, CD4+ T cells, Tregs, and nasal tissues of AR patients, as well as in IL-13-treated NECs. HCP5 promoted Tregs differentiation and proliferation via targeting miR-16/ATXN2L axis. Additionally, HCP5 inhibited IL-13-induced GM-CSF, eotaxin, and MUC5AC production in NECs. HCP5 sponged miR-16 and negatively regulated its expression, and miR-16 targeted ATXN2L and inhibition of miR-16 suppressed IL-13-induced GM-CSF, eotaxin, and MUC5AC expression. HCP5/miR-16/ATXN2L axis mediated Tregs proliferation and functions in AR. Besides, the regulation of IL-13-induced dysfunction of NECs by lncRNA HCP5 depended on miR-16/ATXN2L in the inflammatory response of AR.
PubDate: 2022-06-01
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- Lipopolysaccharide Accelerates Neuropilin-1 Protein Degradation by
Activating the Large GTPase Dynamin-1 in Macrophages-
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Abstract: Abstract Neuropilin-1 (Nrp1) is highly expressed in macrophages and plays a critical role in acute and chronic inflammation-associated diseases, such as sepsis, type II diabetes, and metabolic syndrome. Therefore, it is of importance to understand the regulation of Nrp1. It is known that lipopolysaccharide (LPS) downregulates Nrp1 mRNA levels through the NF-κB signaling in macrophages. However, whether and how LPS regulates Nrp1 protein degradation remain unknown. Here, we show that LPS promotes Nrp1 protein decay through a lysosome-dependent manner. Liver kinase B1 (LKB1)-Rab7 does not mediate this process. However, the large GTPase dynamin-1 (Dyn1) but not Dyn2 is involved in LPS-accelerated Nrp1 degradation. Mechanistically, LPS activates Dyn1 by attenuating p-Dyn1 (Ser774) levels, implying increased Nrp1 endocytosis and consequent degradation. As a result, blocking Nrp1 degradation by Dyn1 siRNA attenuates LPS-induced inflammatory response. Collectively, our study shows that LPS promotes Nrp1 protein degradation via a Dyn1-dependent pathway, revealing a previously uncovered role of Dyn1 in LPS-promoted Nrp1 protein decay.
PubDate: 2022-06-01
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- Quantile-Dependent Expressivity of Serum Interleukin-6 Concentrations as a
Possible Explanation of Gene-Disease Interactions, Gene-Environment
Interactions, and Pharmacogenetic Effects-
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Abstract: Abstract Interleukin 6 (IL-6) is a moderately heritable pleiotropic cytokine whose elevated concentrations in coronary artery disease, peripheral arterial disease, pulmonary arterial hypertension, Eales’ disease, Sjògren’s syndrome, osteoarthritis, adenocarcinoma, neuroblastoma, polymyalgia rheumatica, pulmonary tuberculosis, and enterovirus 71 infection, and following coronary artery bypass graft show larger genetic effects than in unaffected low IL-6 controls. We hypothesize that genetic effects may depend upon whether average IL-6 concentrations are high or low, i.e., quantile-dependent expressivity. Quantile-specific offspring-parent (βOP) and full-sib regression slopes (βFS) were estimated by applying quantile regression to the age- and sex-adjusted serum IL-6 concentrations in families surveyed in the Framingham Heart Study. Quantile-specific heritabilities were calculated as h2 = 2βOP / (1 + rspouse) and h2 = {(1 + 8rspouseβFS)0.5 −1} / (2rspouse)). Heritability (h2 ± SE) of IL-6 concentrations increased from 0.01 ± 0.01 at the 10th percentile (NS), 0.02 ± 0.01 at the 25th (P = 0.009), 0.03 ± 0.01 at the 50th (P = 0.007), 0.04 ± 0.02 at the 75th (P = 0.004), and 0.13 ± 0.05 at the 90th percentile (P = 0.03), or 0.0005 ± 0.0002 for each 1% increase in the offspring’s phenotype distribution (Plinear trend = 0.02) when estimated from βOP and from 0.02 ± 0.02 at the 10th (NS), 0.02 ± 0.02 at the 25th (NS), 0.06 ± 0.02 at the 50th (P = 0.01), 0.12 ± 0.04 at the 75th (P = 0.001), and 0.30 ± 0.03 at the 90th percentile (P < 10−16), or 0.0015 ± 0.0007 for each 1% increase in the sibling phenotype distribution (Plinear trend = 0.02) when estimated from βFS. Thus the heritability of serum IL-6 concentrations is quantile dependent, which may contribute in part to the larger genetic effect size reported for diseases and environmental conditions that elevate IL-6 concentrations vis-à-vis unaffected controls.
PubDate: 2022-06-01
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- Regulatory Role of Nitric Oxide in Cutaneous Inflammation
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Abstract: Abstract Nitric oxide (NO), a signaling molecule, regulates biological functions in multiple organs/tissues, including the epidermis, where it impacts permeability barrier homeostasis, wound healing, and antimicrobial defense. In addition, NO participates in cutaneous inflammation, where it exhibits pro-inflammatory properties via the cyclooxygenase/prostaglandin pathway, migration of inflammatory cells, and cytokine production. Yet, NO can also inhibit cutaneous inflammation through inhibition of T cell proliferation and leukocyte migration/infiltration, enhancement of T cell apoptosis, as well as through down-regulation of cytokine production. Topical applications of NO-releasing products can alleviate atopic dermatitis in humans and in murine disease models. The underlying mechanisms of these discrepant effects of NO on cutaneous inflammation remain unknown. In this review, we briefly review the regulatory role of NO in cutaneous inflammation and its potential, underlying mechanisms.
PubDate: 2022-06-01
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- Expressions of Interleukin-27 in Oral Lichen Planus, Oral Leukoplakia, and
Oral Squamous Cell Carcinoma-
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Abstract: Abstract The present study aimed to detect the expression of interleukin-27 (IL-27) in tissues of oral lichen planus (OLP), oral leukoplakia (OLK), and oral squamous cell carcinoma (OSCC) and to investigate the possible role of IL-27 in the above diseases and whether it was involved in the onset and development of the tumor. Paraffin tissues from patients with OLP, OLK, and OSCC were collected, and the expression of IL-27 in the above tissues was detected by immunohistochemical (IHC) staining. Parameters were obtained from the images by the Image-Pro Plus (IPP) image analysis software, and statistical analysis was performed using relevant data. The expressions of IL-27 were significantly higher in specimens with OLP, OLK, and OSCC than those in the healthy group. In OLP, the expression of IL-27 was positively correlated with the degree of lymphocyte infiltration and basal cell liquefaction while independent of the clinical type. In OLK, the expression of IL-27 was positively correlated with abnormal epithelial cell proliferation. In OSCC, the expression of IL-27 was correlated with the degree of squamous cell differentiation and was independent of gender, TNM stage, and lymphatic metastasis. The expressions of IL-27 were significantly higher in tissues with severe OLP and OLK than that in the control group, while similar to that in highly differentiated OSCC. The expressions of IL-27 were significantly elevated in tissues with OLP, OLK, and OSCC, suggesting that IL-27 might be involved in the development of these diseases and play a role in the carcinogenesis of oral precancerous lesions.
PubDate: 2022-06-01
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- Influence of Pinealectomy and Long-term Melatonin Administration on
Inflammation and Oxidative Stress in Experimental Gouty Arthritis-
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Abstract: Abstract Gout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent inflammation inducers. Melatonin (MLT) is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-inflammatory and antioxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (on the 30th day, single-dose 20 mg/ml, intraperitoneal), MSU + MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU + PINX and MSU + PINX + MLT. PNX procedure was performed on the first day of the study. As compared to the controls, the results showed that MSU administration caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, significant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status) were observed. A statistically significant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were significantly reduced in the MSU + MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of inflammation, were significantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proinflammatory cytokine production.
PubDate: 2022-06-01
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- Kindlin-2 Mediates Lipopolysaccharide-Induced Acute Lung Injury Partially
via Pyroptosis in Mice-
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Abstract: Abstract Acute lung injury (ALI) is characteristic of the wholesale destruction of the lung endothelial barrier, which results in protein-rich lung edema, influx of pro-inflammatory leukocytes, and intractable hypoxemia, contributing to high mortality. Kindlin-2 is involved in the process of tumor- and wound healing-associated inflammation. However, the effects of kindlin-2 on lipopolysaccharide (LPS)-induced ALI and its mechanisms remain unknown. In this study, we found that the concentration of kindlin-2 was elevated in the lungs of ALI mice. The specific deletion of kindlin-2 by kindlin-2 siRNA attenuated the severity of lung injury, which was demonstrated by the reduced number of pro-inflammatory cells in bronchoalveolar lavage fluid and lung wet/dry weight ratio, and ameliorated pathologic changes in the lungs of ALI mice. Furthermore, kindlin-2 siRNA decreased the mRNA levels of pro-inflammatory factors (IL-1β, IL-6, and TNF-α) and the protein levels of pyroptosis-related proteins. In vitro studies confirmed that LPS + ATP promoted the expressions of pro-inflammatory factors and pyroptosis-related proteins, which was prevented by kindlin-2 siRNA pretreatment in endothelial cells (ECs). In conclusion, inhibition of kindlin-2 developes protective effects against LPS-induced ALI and the cytotoxicity of ECs, which may depend on blocking pyroptosis.
PubDate: 2022-06-01
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- Pink1/Parkin-Mediated Mitophagy Regulated the Apoptosis of Dendritic Cells
in Sepsis-
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Abstract: Abstract Dendritic cells (DCs) are vital antigen-presenting cells (APCs) in the immune system, whose apoptosis is closely related to the development of sepsis. Mitophagy is one of the necessary forms of selective autophagy that removes damaged or dysfunctional mitochondria to regulate immunity and inflammation. However, its effect on the apoptosis of DC in sepsis remains unknown. Here, we showed that sepsis activated the apoptosis and mitophagy of DC, and mitophagy had an anti-apoptotic effect on sepsis-induced DC apoptosis. In this study, we used cecal ligation and puncture (CLP) to simulate the pathophysiological state of sepsis. Apoptosis and mitophagy of DC were significantly enhanced in CLP mice compared with controls, and in the Pink1-KO (Pink1-knockout) mice CLP model, the level of apoptosis in DC was further increased while the level of mitophagy was decreased. In addition, more severe mitochondrial dysfunction was exhibited in DC of Pink1-KO mice CLP model compared to wild-type (WT) mice. The results suggest that Pink1/Parkin-mediated mitophagy is activated during sepsis and has an anti-apoptotic effect on DC, which regulates immune functions.
PubDate: 2022-06-01
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- Human Breast Milk–Derived Exosomal miR-148a-3p Protects Against
Necrotizing Enterocolitis by Regulating p53 and Sirtuin 1-
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Abstract: Abstract Necrotizing enterocolitis (NEC) is a gastrointestinal disease that results in the exaggerated intestinal inflammation and injury. Human breast milk–derived exosome (BMEXO) has been reported to relieve NEC, which is closely related to the contained microRNAs (miRNAs). However, which miRNA and whether its synthesized mimic can replace the protection of BMEXO remains unclear. We established a NEC mouse model, and miRNA sequencing was performed to determine the miRNA profiling in BMEXO. The downstream target of miRNA was then confirmed by dual-luciferase reporter assay. Finally, we explored the protective effect of a single miRNA agomir on NEC and its downstream mechanisms. The results revealed that BMEXO treatment exerts a significant protective effect on NEC mice, including inhibiting inflammation and improving intercellular tight junctions. Additionally, as the most abundant miRNA in BMEXO, miR-148a-3p directly targets Tp53 on its 3′ untranslated region (3′ UTR). miR-148a-3p mimic treatment significantly reduces p53 expression and upregulates sirtuin 1 (SIRT1) level in the lipopolysaccharide (LPS)-treated intestinal epithelial IEC6 cells. In addition, decreased nuclear translocation of nuclear factor-κB (NF-κB) and cell apoptosis were observed by miR-148a-3p mimic. Also, delivery of miR-148a-3p agomir in vivo exerts a similar protective role on NEC as BMEXO treatment, accompanied by changes in p53 and SIRT1. Finally, the abolition of the protection of miR-148a-3p agomir on NEC was observed in a Sirt1-deficient (Sirt1+/–) mouse. Collectively, our present study demonstrated that the miR-148a-3p/p53/SIRT1 axis has a considerable protective effect on NEC, and the agomir therapy provides a new treatment strategy for NEC.
PubDate: 2022-06-01
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- MiR-15p-5p Mediates the Coordination of ICAM-1 and FAK to Promote
Endothelial Cell Proliferation and Migration-
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Abstract: Abstract Intercellular adhesion molecule-1 (ICAM-1) in endothelial cells is critical for neutrophil adhesion and transmigration across the endothelium. Focal adhesion kinase (FAK), which controls the turnover of focal adhesion to regulate cell adhesion and migration, plays a role in the resolution of inflammation. However, the coordinated involvement of ICAM-1 and FAK during endothelial inflammation has yet to be elucidated. This study reports that, as part of an inflammatory response, ICAM-1 controls FAK expression in endothelial cells via the microRNA miR-15b-5p. Induction of lung injury by lipopolysaccharide (LPS) resulted in higher levels of FAK expression in inflammatory tissues, while in ICAM-1 knockout mice, FAK expression was reduced in the lungs. FAK expression was also reduced in endothelial cells following ICAM-1 siRNA downregulation. Furthermore, ICAM-1 inhibited miR-15b-5p expression while increasing FAK mRNA and protein expression via binding of miR-15b-5p to the 3′ untranslated region (UTR) of FAK. ICAM-1 inhibited miR-15b-5p promoter activity and hence reduced miR-15b-5p expression. FAK increased endothelial cell proliferation and migration, whereas miR-15b-5p inhibited cell proliferation and migration. These findings indicate that the inflammatory molecule ICAM-1 regulates FAK expression via miR-15b-5p levels, which in turn controls endothelial cell proliferation and migration.
PubDate: 2022-06-01
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- TRIM32 Inhibition Attenuates Apoptosis, Oxidative Stress, and Inflammatory
Injury in Podocytes Induced by High Glucose by Modulating the
Akt/GSK-3β/Nrf2 Pathway-
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Abstract: Abstract Hyperglycemia-induced oxidative stress in podocytes exerts a major role in the pathological process of diabetic nephropathy. Tripartite motif-containing protein 32 (TRIM32) has been reported to be a key protein in the modulation of cellular apoptosis and oxidative stress under various pathological processes. However, whether TRIM32 participates in the regulation of high glucose (HG)-induced injury in podocytes has not been investigated. This work aimed to assess the possible role of TRIM32 in mediating HG-induced apoptosis, oxidative stress, and inflammatory response in podocytes in vitro. Our results showed a marked increase in TRIM32 expression in HG-exposed podocytes and the glomeruli of diabetic mice. Loss-of-function experiments showed that TRIM32 knockdown improves the viability of HG-stimulated podocytes and suppresses HG-induced apoptosis, oxidative stress, and inflammatory responses in podocytes. Further investigation revealed that TRIM32 inhibition enhances the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which is associated with the modulation of the Akt/glycogen synthase kinase-3β (GSK-3β) axis in podocytes following HG exposure. However, Akt suppression abrogated the TRIM32 knockdown-mediated activation of Nrf2 in HG-exposed podocytes. Nrf2 knockdown also markedly abolished the protective effects induced by TRIM32 inhibition o in HG-exposed podocytes. In summary, this work demonstrated that TRIM32 inhibition protects podocytes from HG-induced injury by potentiating Nrf2 signaling through modulation of Akt/GSK-3β signaling. The findings reveal the potential role of TRIM32 in mediating podocyte injury during the progression of diabetic nephropathy.
PubDate: 2022-06-01
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- Metabolomics of Synovial Fluid and Infrapatellar Fat Pad in Patients with
Osteoarthritis or Rheumatoid Arthritis-
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Abstract: Abstract Osteoarthritis (OA) and autoimmune-driven rheumatoid arthritis (RA) are inflammatory joint diseases with complex and insufficiently understood pathogeneses. Our objective was to characterize the metabolic fingerprints of synovial fluid (SF) and its adjacent infrapatellar fat pad (IFP) obtained during the same surgical operation from OA and RA knees. Non-targeted metabolite profiling was performed for 5 non-inflammatory trauma controls, 10 primary OA (pOA) patients, and 10 seropositive RA patients with high-resolution mass spectrometry-based techniques, and metabolites were matched with known metabolite identities. Groupwise differences in metabolic features were analyzed with the univariate Welch’s t-test and the multivariate linear discriminant analysis (LDA) and principal component analysis (PCA). Significant discrimination of metabolite profiles was discovered by LDA for both SF and IFP and by PCA for SF based on diagnosis. In addition to a few drug-derived substances, there were 16 and 13 identified metabolites with significant differences between the diagnoses in SF and IFP, respectively. The pathways downregulated in RA included androgen, bile acid, amino acid, and histamine metabolism, and those upregulated included biotin metabolism in pOA and purine metabolism in RA and pOA. The RA-induced downregulation of androgen and bile acid metabolism was observed for both SF and IFP. The levels of 11 lipid metabolites, mostly glycerophospholipids and fatty acid amides, were also altered by these inflammatory conditions. The identified metabolic pathways could be utilized in the future to deepen our understanding of the pathogeneses of OA and RA and to develop not only biomarkers for their early diagnosis but also therapeutic targets.
PubDate: 2022-06-01
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- Ferroptosis Markers Predict the Survival, Immune Infiltration, and
Ibrutinib Resistance of Diffuse Large B cell Lymphoma-
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Abstract: Abstract Diffuse large B cell lymphoma (DLBCL) is the most common hematological malignancy in adults. Ferroptosis is an iron-dependent programmed cell death caused by lipid peroxidation. However, the potential functions of ferroptosis in the DLBCL prognosis, immune infiltration, and drug resistance remain unknown. Data of DLBCL patients were downloaded from public GEO databases and TCGA cohort. R software was used for analysis. Ferroptosis-related risk score model was constructed using LASSO Cox regression analysis. The prognosis of the model and its association with immune cells infiltration and ibrutinib-resistance were studied by single-sample gene set enrichment analysis (ssGSEA) and correlation analysis. Ferroptosis-related risk score model was constructed with 11 ferroptosis-related genes. DLBCL patients can be divided into high- or low-risk groups with this model. High-risk patients had significant shorter survival (p < 0.001). The area under curve at 3-year was 0.779. Functional enrichment analysis was mainly associated with the immune response. High score patients were positively correlated with immunosuppressive cell infiltration, including macrophages and regulatory T cells, and immunoevasion checkpoints, such as CTLA4, PD-L1, LAG-3, and TIM-3. We also found that tumors with high risk would resist to ibrutinib treatment and uncovered that acetaminophen, as a ferroptosis inducer, inhibited the defined high-risk gene expression in the ibrutinib-resistant DLBCL cell lines. Ferroptosis-related risk score model can predict the overall survival (OS) of DLBCL patients and ibrutinib resistance of ABC-DLBCL cells, which was associated with immunosuppression status within the tumor microenvironment.
PubDate: 2022-06-01
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- Sigma-1 Receptor Alleviates Airway Inflammation and Airway Remodeling
Through AMPK/CXCR4 Signal Pathway-
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Abstract: Abstract Sigma non-opioid intracellular receptor 1 (Sigma-1R) has been proven to play a major role in inflammation and structural remodeling. However, its role in airway inflammation and airway remodeling remains unclear. The purpose of this study aimed to explore the role and mechanism of Sigma-1R in airway remodeling and epithelial-mesenchymal transition (EMT) process in vivo and in vitro. We observed the decrease of Sigma-1R in lung tissue of asthma model. In the mouse model of allergic airway inflammation (AAI), Sigma-1R agonist RPE-084 significantly relieved airway inflammation and airway remodeling, while Sigma-1R antagonist BD1047 (B8562) had opposite effects. Further research showed that RPE-084 treatment increased the expression of pAMPK and inhibited the expression of CXCR4. Furthermore, RPE-084 treatment suppressed the levels of IL-4, IL-5, and IL-13 in BALF. We found that RPE-084 or Sigma-1R overexpression vector treatment regulated cell cycle and inhibited cell proliferation, migration, and EMT process in TGF-β1-induced 16HBE cells. Finally, we confirmed that AMP-activated protein kinase (AMPK) inhibitor compound C or CXCR4 agonist ATI-2341 both reversed the effects of Sigma-1R on TGF-β1-induced 16 HBE cells. In a word, our research shows that Sigma-1R is helpful to improve airway remodeling of asthma, and emphasizes a new candidate molecular for asthma treatment.
PubDate: 2022-06-01
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- Enhanced Responsive Formation of Extracellular Traps in Macrophages
Previously Exposed to Porphyromonas gingivalis-
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Abstract: Abstract Tolerance is defined to be a hyporesponsive state following repeated stimulations with bacteria or their virulence factors and has potential impacts on the development of periodontitis. Recently, macrophages have been reported to release chromatin and antimicrobial peptides to form extracellular traps upon bacterial or chemical stimulations. Thus, we explored the roles and mechanisms of tolerance induced by Porphyromonas gingivalis (P. gingivalis) in macrophage extracellular traps (METs). Tolerance in peritoneal macrophages from mice was triggered by repeated P. gingivalis stimulation. METs were observed using fluorescence microscopy, and the levels of extracellular DNA were determined by microplate reader assays. The expression of p-RAF, p-MEK, and p-ERK was examined by Western blot, and reactive oxygen species (ROS) production was explored using flow cytometry. Moreover, the levels of intracellular Ca2+ were also determined by confocal microscopy to identify the possible mechanisms related to the changes in METs in P. gingivalis–pretreated macrophages. Repeated P. gingivalis stimulation contributed to the formation of METs and increased levels of extracellular DNA (p < 0.05). ROS generation and RAF/MEK/ERK phosphorylation were decreased in P. gingivalis–pretreated macrophages compared with non-pretreated cells (p < 0.05), which was inconsistent with the changes in METs. However, in P. gingivalis–pretreated macrophages, the levels of intracellular Ca2+ were significantly increased compared with the single stimulation group. Additionally, inhibition of intracellular Ca2+ resulted in a decrease in the levels of extracellular DNA in P. gingivalis–pretreated cells (p < 0.05). Taken together, P. gingivalis–pretreated macrophages released more METs, possibly related to the increased levels of intracellular Ca2+.
PubDate: 2022-06-01
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- Aortic Wall Inflammation in the Pathogenesis, Diagnosis and Treatment of
Aortic Aneurysms-
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Abstract: Abstract The role of inflammation in the development of aortic aneurysms is emerging, along with the potential diagnostic and therapeutical potential of this correlation. Abdominal aorta aneurysms have a strong inflammatory substrate since atherosclerosis, which is undoubtedly linked to inflammation, is also a predisposing factor to their formation. Yet, data have emerged that the development of thoracic aorta aneurysms involves several inflammatory pathways, although they were previously referred to as a non-inflammatory disease. Since aortic aneurysms are mainly asymptomatic during their clinical course until their complications—which may be lethal—serum biomarkers for their early diagnosis are a necessity. Studies highlight that inflammation molecules may have a critical role in that direction. In addition, imaging techniques that trace aortic wall inflammation are developed in order to predict aneurysm growth rates and sites vulnerable of rupture. Several anti-inflammatory agents have been also studied in animal models and clinical trials for the treatment of aortic aneurysms. This review highlights the role of inflammation in pathogenesis, diagnosis and treatment of aortic aneurysms.
PubDate: 2022-06-01
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- Protective Effects of 18β-Glycyrrhetinic Acid on Neonatal Rats with
Hyperoxia Exposure-
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Abstract: Abstract Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary complication in preterm infants. Supplemental oxygen is a lifesaving therapeutic measure used for premature infants with pulmonary insufficiency. However, oxygen toxicity is a significant trigger for BPD. Oxidative stress disrupts lung development, accompanied by increased pro-inflammatory cytokines and chemokines expression and immune cells infiltration in lung tissue. Licorice, a typical traditional herbal medicine, is commonly used in the medicine and food industries. 18β-Glycyrrhetinic acid (18β-GA), a primary active ingredient of licorice, has powerful anti-oxidative and anti-inflammatory effects. This study aimed to determine whether 18β-GA has a protective effect on neonatal rats with hyperoxia exposure. Newborn Sprague–Dawley rats were kept in either 21% (normoxia) or 80% O2 (hyperoxia) continuously from postnatal day (PN) 1 to 14. 18β-GA was injected intragastrically at 50 or 100 mg/kg body weight once a day from PN 1 to 14. We examined the body weight and alveolar development and measured ROS level and the markers of pulmonary inflammation. Mature-IL-1β and NF-κB pathway proteins, and the NLRP3 inflammasome, were assessed; concurrently, caspase-1 activity was measured. Our results indicated that hyperoxia resulted in alveolar simplification and decreased bodyweight of neonatal rats. Hyperoxia increased ROS level and pulmonary inflammation and activated NF-κB and the NLRP3 inflammasome. 18β-GA treatment inhibited the activation of NF-κB and the NLRP3 inflammasome, decreased ROS level and pulmonary inflammation, improved alveolar development, and increased the bodyweight of neonatal rats with hyperoxia exposure. Our study demonstrates that 18β-GA has a protective effect on neonatal rats with hyperoxia exposure.
PubDate: 2022-06-01
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- The Priming Potential of Interferon Lambda-1 for Antiviral Defense in the
Oral Mucosa-
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Abstract: Abstract The oral mucosa is one of the first lines of the innate host defense system against microbial invasion. Interferon (IFN) lambda-1 (IFN-λ1), a type III IFN, exhibits type I IFN-like antiviral activity. In contrast to ubiquitously expressed type I IFN receptors, IFN-λ receptor 1 (IFN-λR1), which has higher affinity for type III IFNs than low-affinity interleukin (IL)-10 receptor 2, is mainly expressed on epithelial cells. Although IFN-λ1 has been shown to exert antiviral effects in the respiratory tract, gastrointestinal tract, and skin, the regulation of type III IFN receptor expression and its functions in the oral mucosa remain unclear. We herein showed the expression of IFN-λR1 in human gingival keratinocytes. The expression of IL-6, angiotensin-converting enzyme 2 (a critical molecule for severe acute respiratory syndrome coronavirus 2 infection), and IL-8 in human primary gingival keratinocytes (HGK) were significantly higher following treatments with either type I IFN (IFN-β) or type II IFN (IFN-γ) than with IFN-λ1. However, the IFN-λ1 treatment strongly induced toll-like receptor (TLR) 3 and retinoic acid-inducible gene I (RIG-I), which mainly recognize viral nucleic acids, via the STAT1-mediated pathway. Furthermore, a stimulation with a RIG-I or TLR3 agonist promoted the production of IL-6, IL-8, and IFN-λ in HGK, which was significantly enhanced by a pretreatment with IFN-λ1. These results suggest that IFN-λ1 may contribute to the activation of innate immune responses to oral viral infections by up-regulating the expression of RIG-I and TLR3 and priming their functions in keratinocytes.
PubDate: 2022-06-01
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