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CX-4945 inhibits fibroblast-like synoviocytes functions through the CK2-p53 axis to reduce rheumatoid arthritis disease severity
Int Immunopharmacol. 2023 Apr 13;119:110163. doi: 10.1016/j.intimp.2023.110163. Online ahead of print.ABSTRACTFibroblast-like synoviocytes (FLS) mediate many pathological processes in rheumatoid arthritis (RA), including pannus formation, bone erosion, and inflammation. RA FLS have unique aggressive phenotypes and exhibit several tumor cell-like characteristics, including hyperproliferation, excessive migration and invasion. Casein kinase 2 (CK2) is reportedly overexpressed in numerous tumor types, and targeted inhibition of CK2 has therapeutic benefits for tumors. However, the expression level of CK2 and its functions in ...
Source: International Immunopharmacology - April 15, 2023 Category: Allergy & Immunology Authors: Yanping Luo Yunxuan Lei Xin Guo Dehao Zhu Haiyang Zhang Zizhen Guo Zichong Xu Hanqing Zhao Yebin Xi Xiaochun Peng Lianbo Xiao Zhaojun Wang Xiaoyin Niu Guangjie Chen Source Type: research

Photoacoustic/ultrasound-guided gene silencing: Multifunctional microbubbles for treating adjuvant-induced arthritis
CONCLUSIONS: The theranostic MBs exhibited a TNF-α gene silencing effect under the guidance of CEUS and PAI. The theranostic MBs served as vehicles for delivering siRNA as well as contrast agents for CEUS and PAI.PMID:37012868 | DOI:10.1016/j.intimp.2023.109978
Source: International Immunopharmacology - April 4, 2023 Category: Allergy & Immunology Authors: Chenyang Zhao Rui Zhang Sirui Liu Xuelan Li Desheng Sun Yuxin Jiang Meng Yang 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

Geniposide restricts angiogenesis in experimentary arthritis via inhibiting Dnmt1-mediated PTEN hypermethylation
In this study, human umbilical vein endothelial cells (HUVEC) and adjuvant arthritis (AA) rat models were performed to research in vitro and in vivo. The results showed that GE treatment significantly reduced synovitis and angiogenesis in AA rats, which may be associated with the increased expression of PTEN with GE treatment. Meanwhile, the hypermethylation of PTEN accompanied by the over-expression of DNA methyltransferases (Dnmts) was demonstrated in TNF-α-induced HUVEC and AA rats. Knockdown of Dnmt1 by Dnmt1- siRNA significantly inhibited the tube formation of HUVEC in vitro. GE significantly restricted the angiogene...
Source: International Immunopharmacology - July 31, 2022 Category: Allergy & Immunology Authors: Yanhong Bu Hong Wu Ran Deng Yan Wang Source Type: research

Agrimophol suppresses RANKL-mediated osteoclastogenesis through Blimp1-Bcl6 axis and prevents inflammatory bone loss in mice.
In this study, we found that AGR inhibited RANKL-induced osteoclastogenesis, bone-resorption, F-actin ring formation, and the mRNA expression of osteoclast-associated genes such as CTSK, TRAP, MMP-9, and ATP6v0d2 in vitro. In addition, AGR suppressed RANKL-induced expression of c-Fos and NFATc1. However, AGR treatment did not affect NF-κB activation and MAPKs phosphorylation in RANKL-stimulated BMMs, which implicated that AGR might not influence the initial expression of NFATc1 mediated by NF-κB and MAPKs signaling. Our results further indicated that AGR did not alter phosphorylation levels of GSK3β and the expression o...
Source: International Immunopharmacology - November 13, 2020 Category: Allergy & Immunology Authors: Cao J, Wang S, Wei C, Lin H, Zhang C, Gao Y, Xu Z, Cheng Z, Sun WC, Wang HB Tags: Int Immunopharmacol Source Type: research

Nanoparticle-facilitated delivery of BAFF-R siRNA for B cell intervention and rheumatoid arthritis therapy.
Abstract The present study was designed to explore the effects of B-cell activating factor receptor (BAFF-R) siRNA encapsulated nanoparticles on collagen-induced arthritis (CIA). BAFF-R siRNA encapsulated nanoparticles (NP-siBAFF-R) were constructed using a double emulsion method and was characterized by dynamic light scattering and transmission electron microscopy. Cellular uptake of nanoparticles was determined using flow cytometry. The CIA mouse model was established and the mice were intravenously injected with nanoparticles. NP-siBAFF-R effectively decreased the expression of BAFF-R in B cells and facilitated...
Source: International Immunopharmacology - August 27, 2020 Category: Allergy & Immunology Authors: Wu H, Su S, Wu Y, Wu Y, Zhang Z, Chen Q Tags: Int Immunopharmacol Source Type: research

Up-regulation of miR-365 promotes the apoptosis and restrains proliferation of synoviocytes through downregulation of IGF1 and the inactivation of the PI3K/AKT/mTOR pathway in mice with rheumatoid arthritis.
CONCLUSION: Our study presents that up-regulation of miR-365 drives on apoptosis and restrains proliferation of synoviocytes in RA through downregulation of IGF1 and the inhibition of the PI3K/AKT/mTOR pathway. Thus, miR-365 may be a potential candidate for treatment of RA. PMID: 31881377 [PubMed - as supplied by publisher]
Source: International Immunopharmacology - December 23, 2019 Category: Allergy & Immunology Authors: Wang X, Gong S, Pu D, Hu N, Wang Y, Fan P, Zhang J, Lu X Tags: Int Immunopharmacol Source Type: research

CXCL16/CXCR6 axis promotes bleomycin-induced fibrotic process in MRC-5 cells via the PI3K/AKT/FOXO3a pathway.
CONCLUSIONS: CXCL16/CXCR6 axis promotes proliferation and collagen production of MRC-5 cells by the PI3K/AKT/FOXO3a signaling pathway, and inhibition of the CXCL16/CXCR6 axis may provide a new therapeutic strategy targeting pulmonary fibrosis. PMID: 31753588 [PubMed - as supplied by publisher]
Source: International Immunopharmacology - November 17, 2019 Category: Allergy & Immunology Authors: Ma Z, Yu R, Zhu Q, Sun L, Jian L, Wang X, Zhao J, Li C, Liu X Tags: Int Immunopharmacol 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

Arsenic trioxide improves Treg and Th17 balance by modulating STAT3 in treatment-na ïve rheumatoid arthritis patients.
CONCLUSIONS: These data indicate that As2O3 may be a potential immune modulator for treatment-naïve RA patients that helps to balance of Treg and Th17 cells through modulating STAT3. PMID: 31177080 [PubMed - as supplied by publisher]
Source: International Immunopharmacology - June 5, 2019 Category: Allergy & Immunology Authors: Li C, Zhang J, Wang W, Wang H, Zhang Y, Zhang Z Tags: Int Immunopharmacol Source Type: research

Sinomenine inhibits fibroblast-like synoviocyte proliferation by regulating α7nAChR expression via ERK/Egr-1 pathway.
In conclusion, the expression of α7nAChR involved in the aggressive proliferation of FLS induced by TNF-α and was regulated by ERK/Egr-1 signal pathway. SIN inhibited FLS proliferation and α7nAChR expression through inhibiting ERK/Egr-1 signal pathway, this may contribute to the anti-inflammatory and anti-arthritic effect of SIN. PMID: 29367088 [PubMed - as supplied by publisher]
Source: International Immunopharmacology - January 20, 2018 Category: Allergy & Immunology Authors: Yi L, Lyn YJ, Peng C, Zhu RL, Bai SS, Liu L, Wang PX, Zhou H, Dong Y Tags: Int Immunopharmacol Source Type: research

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