(Z)-5-(4-methoxybenzylidene) thiazolidine-2, 4-dione ameliorates the adjuvant-induced arthritis via inhibiting the migration of macrophage and down-regulating the cytokine mRNA expression.
In our previous study, we have demonstrated that (Z)-5-(4-methoxybenzylidene) thiazolidine-2, 4-dione (SKLB010), a novel analogue of thiazolidinediones, showed protection against concanavalin A (Con A)-induced hepatitis via inhibiting the migration of macrophages and the expression of pro-inflammatory mediators. In present study, Transwell assay was applied to study the effects of SKLB010 on macrophage-like Raw264.7 cell migration and we investigated the effects of SKLB010 on NO generation in vitro. We also studied in vivo effects of SKLB010 on adjuvant-induced arthritis in Lewis rats by oral administration. It was proved that SKLB010 depressed cells migration and the production of NO in Raw264.7 cells in a dose-dependent way. Our results also indicated that oral administration of 50 mg/kg SKLB010 markedly resulted in a clear suppression of clinical signs compared to untreated groups, showing as markedly reduction of paw swelling and inhibition of body weight decreasing. The improvement in disease severity was accompanied by suppression of CD68-positive cells in knee joint and by inhibition of production in pro-inflammatory cytokines of TNF-α, IL-1β and IL-6 in serum. The elevated TNF-α, IL-1β and iNOS mRNA expression in tissue were down-regulated after treatment with SKLB010. SKLB010 also significantly inhibited the histological progress of RA. These data indicate that SKLB010 is a potent anti-inflammatory therapeutic agent targeting the inflammatory response of macrophages.
Ma
Yinghua
Y
State Key Laboratory of Biotherapy and Cancer Centre, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Wang
Xianhuo
X
Wu
Xiaohua
X
Wei
Xin
X
Ma
Liang
L
Zheng
Hao
H
Qi
Baowen
B
Zhu
Wei
W
Luo
Youfu
Y
Wei
Yuquan
Y
Chen
Lijuan
L
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D002464:Cell Migration Inhibition / Q000187:drug effects*; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000032:analysis / Q000378:metabolism; D051381:Rats; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood; D000097382:CD68 Molecule
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C546799:5-(4-methoxybenzylidene)thiazolidine-2,4-dione; C067980:CD68 antigen, human; D000097382:CD68 Molecule