caa a22 4500 445885149 CHVBK 20180317145557.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00011-011-0338-1 doi (NATIONALLICENCE)springer-10.1007/s00011-011-0338-1 Inhibition of inflammatory mediators and related signaling pathways by macrophage-stimulating protein in rheumatoid arthritis synovial fibroblasts [Elektronische Daten] [Xiang-min Tong, Jian-chao Wang, Yuedi shen, Jun-jun Xie, Jun-yu Zhang, Jie Jin] Objective: To evaluate the mechanism of macrophage-stimulating protein (MSP)-mediated inhibition of inflammatory cytokine and chemokine production in rheumatoid arthritis synovial fibroblasts (RASF). Materials and methods: RASF were treated with different concentrations (0, 0.5, 1, 5 and 10ng/ml) of MSP with or without 1μg/mL lipopolysaccharide (LPS). The protein expressions of IL-1β, TNF-α, IL-18, MIP-1, MCP-1, RANTES and PGE2 were analyzed by enzyme-linked immunosorbent assays (ELISA). The total nitric oxide (NO) concentration was determined using the Griess reaction. The protein expressions of iNOS, COX-2, NF-κB(p-p65), IKB-α, IKB-β, p-P38, p-Erk1/2 (P-P42/44) and p-AKT were detected by Western blotting. Results: MSP markedly inhibited expression of inflammatory cytokines (IL-1β, TNF-α and IL-18), chemokines (MIP-1, MCP-1 and RANTES) and iNOS, NO, COX-2 and PGE2 in RASF stimulated by LPS. MSP treatment decreased expressions of p-IκBα, p-IKBβ and p-P65 in RASF in a concentration-dependent manner. Expressions of p-AKT, p-p38 and p-Erk1/2 were also inhibited markedly in RASF stimulated by LPS after treatment with MSP in a concentration-dependent manner. Conclusion: MSP could inhibit the inflammatory cycle by suppressing inflammatory mediators and activation of NF-κB as well. The inhibitory effect of MSP on LPS-stimulated RASF may act through suppression of multiple signals such as the PI3K/AKT and/or MAPK pathways. Springer Basel AG, 2011 Rheumatoid arthritis nationallicence MSP nationallicence Inflammatory mediators nationallicence PI3K/AKT nationallicence MAPK nationallicence NF-κB nationallicence Tong Xiang-min Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, People's Republic of China aut Wang Jian-chao Department of Clinical Laboratory, The Xinhua Hospital, 310015, Hangzhou, People's Republic of China aut shen Yuedi The Second People's Hospital of Hangzhou, 310006, Hangzhou, People's Republic of China aut Xie Jun-jun The Second People's Hospital of Hangzhou, 310006, Hangzhou, People's Republic of China aut Zhang Jun-yu The Lishui People's Hospital, 325005, Lishui, People's Republic of China aut Jin Jie Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, People's Republic of China aut Inflammation Research SP Birkhäuser Verlag Basel 60/9(2011-09-01), 823-829 1023-3830 60:9<823 2011 60 11 https://doi.org/10.1007/s00011-011-0338-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-011-0338-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tong Xiang-min Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Wang Jian-chao Department of Clinical Laboratory, The Xinhua Hospital, 310015, Hangzhou, People's Republic of China aut NATIONALLICENCE 700 1- shen Yuedi The Second People's Hospital of Hangzhou, 310006, Hangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Xie Jun-jun The Second People's Hospital of Hangzhou, 310006, Hangzhou, People's Republic of China aut NATIONALLICENCE 700 1- Zhang Jun-yu The Lishui People's Hospital, 325005, Lishui, People's Republic of China aut NATIONALLICENCE 700 1- Jin Jie Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, People's Republic of China aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/9(2011-09-01), 823-829 1023-3830 60:9<823 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer