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ATRA ameliorates fibrosis by suppressing the pro-fibrotic molecule Fra2/AP-1 in systemic sclerosis
In this study, the pro-fibrotic effect of Fra2 in SSc is confirmed. SSc dermal fibroblasts and bleomycin-induced fibrotic tissues of SSc animals exhibit increased levels of Fra2. Inhibition of Fra2 expression in SSc dermal fibroblasts with Fra2 siRNA markedly decreased collagen I expression. ATRA reduced the expressions of Fra2, collagen I, and α-smooth muscle actin(α-SMA) in SSc dermal fibroblasts and bleomycin-induced fibrotic tissues of SSc mice. In addition, chromatin immunoprecipitation and dual-luciferase assays demonstrated that retinoic acid receptor RARα binds to the FRA2 promoter and modulates its transcriptio...
Source: International Immunopharmacology - June 18, 2023 Category: Allergy & Immunology Authors: Zixin Pi Jiani Liu Yangfan Xiao Xinglan He Ruixuan Zhu Rui Tang Xiangning Qiu Yi Zhan Zhuotong Zeng Yaqian Shi Rong Xiao Source Type: research

Acid sensor ASIC1a induces synovial fibroblast proliferation via Wnt/ β-catenin/c-Myc pathway in rheumatoid arthritis
Int Immunopharmacol. 2022 Oct 21;113(Pt A):109328. doi: 10.1016/j.intimp.2022.109328. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia and progressive joint destruction in the middle and late stages. Notably, activated rheumatoid arthritis synovial fibroblasts (RASFs) exhibit tumor-like features, including an increased proliferation rate that largely contributes to pannus formation and joint destruction. Our previous studies have demonstrated that acid-sensing ion channel 1a (ASIC1a) was highly expressed in RASFs, and acidic microenvironment of sy...
Source: International Immunopharmacology - October 24, 2022 Category: Allergy & Immunology Authors: Yayun Xu Zheng Lu Yian Ling Ruirui Hou Jingjing Tao Ge Deng Xiaoling Xu Xuewei Chen Jingjing Ruan Yihao Zhang Xiaoqing Peng Feihu Chen Source Type: research

BMP9 inhibits the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis via the PI3K/AKT signaling pathway.
In this study, we explored the function and underlying mechanisms of BMP9 in the proliferation and migration of RA FLSs. We found that BMP9 expression was significantly downregulated in the synovial tissues of RA patients, compared with those of OA patients; BMP9 expression was also low in adjuvant-induced arthritis (AA) samples. Additionally, inhibition of BMP9 expression by BMP9 siRNA increased the proliferation of AA FLSs, and the expression of c-Myc, Cyclin D1, MMP-2, and MMP-9, but not TIMP-1, in AA FLSs. However, AA FLSs transfected with the overexpression vector PEX-3-BMP9 showed reduced proliferation and expression...
Source: International Immunopharmacology - June 12, 2019 Category: Allergy & Immunology Authors: Song B, Li XF, Yao Y, Xu QQ, Meng XM, Huang C, Li J Tags: Int Immunopharmacol Source Type: research

1,25 ‑Dihydroxyvitamin D regulates macrophage polarization and ameliorates experimental inflammatory bowel disease by suppressing miR-125b.
This study aimed to explore whether 1,25(OH)2D3 modulates macrophage polarization in inflammation. Peripheral blood mononuclear cells and colitis mice were treated with 1,25(OH)2D3. Macrophages were transfected with siRNA-vitamin D receptor (VDR) or miR-125b mimic or inhibitor, and 1,25(OH)2D3-pretreated colitis mice were injected with a miR-125b agomir. The distribution of macrophage subsets and macrophage subtype characteristics was analyzed. As expected, 1,25(OH)2D3 transformed lipopolysaccharide-induced M1 macrophages to the M2 subset, downregulated tumor necrosis factor-α and interleukin (IL)-6 expression and interfe...
Source: International Immunopharmacology - December 9, 2018 Category: Allergy & Immunology Authors: Zhu X, Zhu Y, Li C, Yu J, Ren D, Qiu S, Nie Y, Yu X, Xu X, Zhu W Tags: Int Immunopharmacol Source Type: research

MicroRNA-21 silencing prolongs islet allograft survival by inhibiting Th17 cells.
In this study, we examined the impact of systemic administration of miR-21 inhibitor on allografts in a pancreatic islet transplantation model. We showed that specific miR-21 silencing in vivo significantly prolonged allograft survival (median survival time (MST) 21 days with antagomiR-21 vs 13 days for the control, p < 0.05), and the change was associated with a decrease in Th17 cells (~3-fold) and an increase in B10 cells (~2.4-fold). Moreover, we found that miR-21-silenced B cells mediate this protective role through pro-inflammatory Th17 responses in an IL-10-dependent fashion. Thus, we have revealed a novel...
Source: International Immunopharmacology - November 28, 2018 Category: Allergy & Immunology Authors: Wang H, Fan H, Tao J, Shao Q, Ding Q Tags: Int Immunopharmacol Source Type: research

A novel role for RGMa in modulation of bone marrow-derived dendritic cells maturation induced by lipopolysaccharide.
Abstract Repulsive guidance molecule a (RGMa) is known to mediate immune responses and has been indicated to modulates T cell activation and autoimmune diseases by dendritic cells (DCs), which hints its significant function in the latter cells. The aim of our study, therefore, was to evaluate the function of RGMa in DC maturation. We found that small interfering RNA (siRNA) successfully silenced the expression of RGMa in DCs. Even after LPS stimulation, RGMa-silenced DCs displayed an immature morphology, characterized by small, round cells with a few cell processes and organelles, and many pinocytotic vesicles. In...
Source: International Immunopharmacology - February 17, 2016 Category: Allergy & Immunology Authors: Xu X, Gao Y, Shan F, Feng J Tags: Int Immunopharmacol Source Type: research

Curcumin induces apoptotic cell death of activated human CD4+ T cells via increasing endoplasmic reticulum stress and mitochondrial dysfunction.
Abstract Curcumin, a natural polyphenolic antioxidant compound, exerts well-known anti-inflammatory and immunomodulatory effects, the latter which can influence the activation of immune cells including T cells. Furthermore, curcumin can inhibit the expression of pro-inflammatory cytokines and chemokines, through suppression of the NF-κB signaling pathway. The beneficial effects of curcumin in diseases such as arthritis, allergy, asthma, atherosclerosis, diabetes and cancer may be due to its immunomodulatory properties. We studied the potential of curcumin to modulate CD4+ T cells-mediated autoimmune disease, by e...
Source: International Immunopharmacology - February 14, 2013 Category: Allergy & Immunology Authors: Zheng M, Zhang Q, Joe Y, Lee BH, Ryu DG, Kwon KB, Ryter SW, Chung HT Tags: Int Immunopharmacol Source Type: research