Rosiglitazone-mediated dendritic cells ameliorate collagen-induced arthritis in mice

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• 作者：Sei-Hee Byun^a ; ¹ ; Jun-Ho Lee^a ; ^b ; ¹ ; Nam-Chul Jung^b ; Hyun-Ji Choi^a ; Jie-Young Song^c ; Han Geuk Seo^d ; Jinjung Choi^e ; Sang Youn Jung^e ; Sangjin Kang^a ; Yong-Soo Choi^a ; Ji Hyung Chung^a ; Dae-Seog Lim^a ; ^{dslim@cha.ac.kr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Autoimmune diseases ; Dendritic cells ; Treg cells ; Mouse models RA
• 刊名：Biochemical Pharmacology
• 出版年：2016
• 出版时间：1 September 2016
• 年：2016
• 卷：115
• 期：Complete
• 页码：85-93
• 全文大小：2282 K

文摘

Rosiglitazone is a selective ligand for peroxisome proliferator-activated receptor-gamma (PPAR-γ), which serves diverse biological functions. A number of autoimmune disease models have been used to examine the anti-inflammatory and immunosuppressive effects of tolerogenic dendritic cells (tDCs). The aim of the present study was to investigate whether rosiglitazone-mediated DC (Rosi-DC) therapy suppressed arthritis in a collagen-induced arthritis (CIA) mouse model.

Rosi-DCs were generated by treating immature DCs with TNF-α, type II collagen, and rosiglitazone. CIA mice then received subcutaneously (s.c.) two injections of Rosi-DCs. The severity of arthritis was then assessed histopathologically. The phenotypes of the DC and regulatory T (Treg) cell populations in CIA mice were determined by flow cytometry and the effect of Rosi-DCs on the secretion of autoimmunity-inducing cytokines was examined by ELISA.

Rosi-DCs expressed lower levels of DC-related surface markers than mature DCs. Histopathological examination revealed that the degree of inflammation in the paws of Rosi-DC-treated mice was much lower than that in the paws of PBS-treated CIA mice.

Taken together, these results clearly show that rosiglitazone-mediated DCs ameliorate CIA, most likely via the induction of antigen-specific Treg cells.