Novel HIF-1 α Inhibitor AMSP-30m Mitigates the Pathogenic Cellular Behaviors of Hypoxia-Stimulated Fibroblast-Like Synoviocytes and Alleviates Collagen-Induced Arthritis in Rats via Inhibiting Sonic Hedgehog Pathway
AbstractSynovial hypoxia-inducible factor 1 α (HIF-1α) is a prospective therapeutic target for rheumatoid arthritis (RA). AMSP-30 m, a novel HIF-1α inhibitor, was reported to have notable anti-arthritic effects in rats with adjuvant-induced arthritis. However, its roles in inhibiting the pathogenic behaviors of fibroblast-like synoviocyte s (FLS) and the involved mechanisms remain unknown. Here, AMSP-30 m inhibited proliferation and induced apoptosis in hypoxia-induced RA FLS (MH7A cell line), as evidenced by decreased cell viability, reduced Ki67-positive cells, G0/G1 phase arrest, lowered C-myc and Cyclin D1 protein...
Source: Inflammation - November 25, 2023 Category: Allergy & Immunology Source Type: research
Long Non-Coding RNA ANRIL Regulates Inflammatory Factor Expression in Ulcerative Colitis Via the miR-191-5p/SATB1 Axis
This study revealed that ANRIL is involved in the progression of UC by inhibiting IL-6 and TNF- α via miR-191-5P/SATB1 axis. We found that in patients with UC, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were significantly overexpressed in inflamed colon sites, whereas ANRIL was significantly under-expressed and associated with disease severity. The downregulation of ANRIL resu lted in the increased expression of IL-6 and TNF-α in LPS-treated FHCs. ANRIL directly targeted miR-191-5p, thereby inhibiting its expression and augmenting SATB1 expression. Moreover, overexpression of miR-191-5p abolished ANRIL-me...
Source: Inflammation - November 21, 2023 Category: Allergy & Immunology Source Type: research
Galectin-3 Mediates Endotoxin Internalization and Caspase-4/11 Activation in Tubular Epithelials and Macrophages During Sepsis and Sepsis-Associated Acute Kidney Injury
The objective of this study was to investigate whether Galectin-3 (Gal3) could promote the uptake of LPS by governing RAGE or administering endocytosis, consequently activating Caspase 4/11 and mediating pyroptosis in sepsis-associated acute kidney injury (SA-AKI). By pinpointing Gal3, LPS, and EEA1 (endosome-marker) or LAMP1 (lysosome-marker) respectively, immunofluorescence discovered that Gal3 and LPS were mainly aggregated in early endosomes initially and translocated into lysosomes afterwards. In cells and animal models, Gal3 and the Caspase-4/11 pathways were simultaneously activated, and the overexpression of Gal3 c...
Source: Inflammation - November 18, 2023 Category: Allergy & Immunology Source Type: research
The Effect of Glycine and N-Acetylcysteine on Oxidative Stress in the Spinal Cord and Skeletal Muscle After Spinal Cord Injury
AbstractOxidative stress is a frequently occurring pathophysiological feature of spinal cord injury (SCI) and can result in secondary injury to the spinal cord and skeletal muscle atrophy. Studies have reported that glycine and N-acetylcysteine (GlyNAC) have anti-aging and anti-oxidative stress properties; however, to date, no study has assessed the effect of GlyNAC in the treatment of SCI. In the present work, we established a rat model of SCI and then administered GlyNAC to the animals by gavage at a dose of 200 mg/kg for four consecutive weeks. The BBB scores of the rats were significantly elevated from the first to the...
Source: Inflammation - November 17, 2023 Category: Allergy & Immunology Source Type: research
SLAMF7 Promotes Foam Cell Formation of Macrophage by Suppressing NR4A1 Expression During Carotid Atherosclerosis
AbstractMacrophage-derived lipid-laden foam cells from the subendothelium play a crucial role in the initiation and progression of atherosclerosis. However, the molecule mechanism that regulates the formation of foam cells is not completely understood. Here, we found that SLAMF7 was upregulated in mice bone marrow –derived macrophages and RAW264.7 cells stimulated with oxidized low-density lipoprotein (ox-LDL). SLAMF7 promoted ox-LDL-mediated macrophage lipid accumulation and M1-type polarization. SLAMF7 deficiency reduced serum lipid levels and improved the lesions area of carotid plaque and aortic arch in high-fat diet...
Source: Inflammation - November 16, 2023 Category: Allergy & Immunology Source Type: research
The Use of Microbial Modifying Therapies to Prevent Psoriasis Exacerbation and Associated Cardiovascular Comorbidity
AbstractPsoriasis has emerged as a systemic disease characterized by skin and joint manifestations as well as systemic inflammation and cardiovascular comorbidities. Many progresses have been made in the comprehension of the immunological mechanisms involved in the exacerbation of psoriatic plaques, and initial studies have investigated the mechanisms that lead to extracutaneous disease manifestations, including endothelial disfunction and cardiovascular disease. In the past decade, the involvement of gut dysbiosis in the development of pathologies with inflammatory and autoimmune basis has clearly emerged. More recently, ...
Source: Inflammation - November 13, 2023 Category: Allergy & Immunology Source Type: research
Human Umbilical Cord Mesenchymal Stem Cells Repair Endothelial Injury and Dysfunction by Regulating NLRP3 to Inhibit Endothelial Cell Pyroptosis in Kawasaki Disease
This study examined whether Huc-MSCs inhibited endothelial inflammation and improved endothelial function in KD through constructing cell andin vivo animal KD vasculitis models. The pyroptosis factor NOD-like receptor protein 3 (NLRP3) was involved in the inflammatory process in the acute phase of KD. After tail vein injection of Huc-MSCs, inflammatory cell infiltration and the expression of pyroptosis-related proteins in the LCWE-induced KD mouse vasculitis model were significantly reduced.In vitro, NLRP3-dependent pyroptosis successfully induced human umbilical vein endothelial cell (HUVEC) damage. Huc-MSCs effectively i...
Source: Inflammation - November 10, 2023 Category: Allergy & Immunology Source Type: research
IRF4 Participates in Pulmonary Fibrosis Induced by Silica Particles through Regulating Macrophage Polarization and Fibroblast Activation
In this study, RNA-seq analysis identified the upregulated expression ofIRF4 in fibrotic lung tissues of mice exposed to silica particles. And we verified the increased expression ofIRF4 in SiO2-treated macrophages and TGF- β1-treated fibroblasts. We further found that the down-regulation ofIRF4 impeded the macrophage polarization and the release of pro-fibrotic factors. Moreover, the down-regulation ofIRF4 alleviated the migration, invasion, and the expression of fibrotic molecules in fibroblasts. Using ChIP-qPCR assay, we confirmed thatIRF4 regulated the transcriptional activity of theIL-17A promoter, thus stimulated fi...
Source: Inflammation - November 8, 2023 Category: Allergy & Immunology Source Type: research
