Attenuation of experimental colonic injury by thiazolidinedione agents.
OBJECTIVE
We investigated the potential use and action mechanisms of thiazolidinedione (TZD) agonists for peroxisome proliferator-activated receptor-gamma, 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.
Takaki
K
K
Second Department of Medicine, Kurume University School of Medicine, Asahi-machi 67, Kurume 830-0011, Japan.
Mitsuyama
K
K
Tsuruta
O
O
Toyonaga
A
A
Sata
M
M
D000818:Animals; D003106:Colon / Q000293:injuries*; D003108:Colonic Diseases / Q000188:drug therapy* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D047495:PPAR gamma / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*
D016207:Cytokines; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D047495:PPAR gamma; D050796:STAT3 Transcription Factor; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione