Objective: We investigated the potential use and action mechanisms of thiazolidinedione (TZD) agonists for peroxisome proliferator-activated
receptor-γ, namely pioglitazone and netoglitazone, during dextran sulfate sodium (DSS)-induced colitis in mice.
Methods: Colitis was induced by the drinking of 2.5% DSS for 7 days. In the prophylactic protocol, pioglitazone or netoglitazone was
administered 2 days before the first DSS exposure and repeated daily for a total of 10 doses. In the therapeutic protocol,
pioglitazone was administered 2 days after the first DSS exposure and repeated daily for a total of 10 doses. The effect of
pioglitazone on proinflammatory cytokine signaling was examined both in vivo and in vitro.
Results: Colitis was significantly attenuated by both pioglitazone and netoglitazone in the prophylactic protocol and by pioglitazone
in the therapeutic protocol. The improvement of colitis by pioglitazone was associated with decreased colonic interleukin-6,
and phospho-signal transducer and activator of transcription-3 levels. In vitro experiments revealed that culturing lamina propria mononuclear cells in the presence of pioglitazone down-regulated the production
of interleukin-6.
Conclusions: These TZD agents should be considered for use as new therapeutic agents in intestinal inflammation such as inflammatory bowel
disease. TZD-induced improvement in inflammation is explained, in part, by down-regulation of proinflammatory cytokine signaling.
Key words. Cytokines - Inflammatory bowel disease - PPAR-γ - STAT - Thiazolidinediones
Received 23 February 2005; returned for revision 15 September 2005; accepted by I. Ahnfelt-Rønne 15 September 2005