PMID- 32594339 OWN - NLM STAT- MEDLINE DCOM- 20210428 LR - 20210428 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 473 IP - 1-2 DP - 2020 Oct TI - Inflammation suppression by dexamethasone via inhibition of CD147-mediated NF-kappaB pathway in collagen-induced arthritis rats. PG - 63-76 LID - 10.1007/s11010-020-03808-5 [doi] AB - Dexamethasone (Dex) exhibits broad-spectrum anti-inflammatory effects in chronic destructive rheumatoid arthritis. We present in vivo and in vitro evidence supporting the preventive effects and underlying mechanisms of Dex on collagen-induced arthritis (CIA)-induced synovial injuries. After successful induction of CIA, Wistar rats were administered Dex intraperitoneally (1 mg/kg) three times a week for more than 2 weeks. In vivo, paw swelling, arthritis scores, and histological evaluations were analyzed to determine the therapeutic effects of Dex on the progression of arthritis. In vitro, CIA fibroblast-like synoviocytes (FLSs) were treated for 48 h with vehicle (control group), 10 ng/mL IL-1alpha (IL-1alpha group), 10 ng/mL IL-1alpha + 10 muM Dex (Dex group), or 10 ng/mL IL-1alpha + 10 mug/mL anti-CD147 antibody (anti-CD147 group). Evaluations of FLSs proliferation, cell cycle, migration, gene expression of Cyclin D1, p27, p57, interleukin (IL)-1beta, IL-6, IL-17, tumor necrosis factor (TNF)-alpha, CD147, CypB, matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13, ROS generation, protein expression of NF-kappaB and CD147, and translocation of NF-kappaB p65 were all conducted. The in vivo results showed that arthritis intensity was attenuated in the Dex-treated group. The in vitro findings demonstrated that treatment with Dex induced G0/G1 arrest and suppressed proliferation, migration, gene expression of IL-1beta, IL-6, IL-17, TNF-alpha, CD147, CypB, MMP-3, MMP-9, and MMP-13, ROS generation and protein expression of NF-kappaB and CD147. Translocation of NF-kappaB p65 was inhibited by both Dex and anti-CD147 monoclonal antibody treatment. We offer molecular evidence of the anti-rheumatism efficacy Dex through hindrance to CD147, splendidly stabilization of the oxidative stress by downregulating the NF-kappaB signaling pathway. FAU - Wang, Qishan AU - Wang Q AD - Departments of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. FAU - Xu, Bingxin AU - Xu B AD - Departments of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. FAU - Fan, Kaijian AU - Fan K AD - Departments of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. FAU - Wu, Jing AU - Wu J AD - Departments of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. FAU - Wang, Tingyu AU - Wang T AUID- ORCID: 0000-0001-5000-7890 AD - Departments of Pharmacy, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. drtywang@163.com. LA - eng GR - 81874011/National Natural Science Foundation of China/ GR - 81572104/National Natural Science Foundation of China/ GR - 81301531/National Natural Science Foundation of China/ GR - 18140903502/Science and Technology Commission of Shanghai Municipality/ PT - Journal Article DEP - 20200627 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Cytokines) RN - 0 (Rela protein, rat) RN - 0 (Transcription Factor RelA) RN - 136894-56-9 (Basigin) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Animals MH - Arthritis, Experimental/drug therapy/*metabolism/pathology MH - Basigin/*metabolism MH - Cytokines/biosynthesis MH - Dexamethasone/*pharmacology MH - Gene Expression Regulation/*drug effects MH - Male MH - Rats MH - Rats, Wistar MH - Signal Transduction/*drug effects MH - Transcription Factor RelA/*metabolism OTO - NOTNLM OT - Arthritis OT - CD147 OT - Dexamethasone OT - Inflammation OT - NF-kappab OT - ROS EDAT- 2020/07/01 06:00 MHDA- 2021/04/29 06:00 CRDT- 2020/06/29 06:00 PHST- 2020/04/14 00:00 [received] PHST- 2020/06/18 00:00 [accepted] PHST- 2020/07/01 06:00 [pubmed] PHST- 2021/04/29 06:00 [medline] PHST- 2020/06/29 06:00 [entrez] AID - 10.1007/s11010-020-03808-5 [pii] AID - 10.1007/s11010-020-03808-5 [doi] PST - ppublish SO - Mol Cell Biochem. 2020 Oct;473(1-2):63-76. doi: 10.1007/s11010-020-03808-5. Epub 2020 Jun 27.