The PPARgamma agonist rosiglitazone impairs colonic inflammation in mice with experimental colitis.
Various animal models showed that peroxisome proliferator-activated receptor (PPAR)gamma agonists, when given as a gavage shortly preceding colitis induction, protect against inflammatory bowel disease (IBD). We have examined the effects of 16 days rosiglitazone treatment via the diet prior to dextran sodium sulphate (DSS)-induced colitis in mice. After 7 days DSS in the drinking water, rosiglitazone-fed mice had lost significantly more weight than control mice. Rosiglitazone-treated mice had more diarrhea, weight of colon and spleen were increased, and length of colon was decreased. Histology showed that rosiglitazone-treated mice had more severe colitis, mainly caused by more ulceration, crypt loss, and edema. Immunofluorescence showed a loss of tight junction structure Zonula Occludens protein 1 (ZO-1) in colons of rosiglitazone-treated mice as compared to control mice. Also, serum amyloid P component (SAP) concentrations in plasma were increased. However, concentrations of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in colon homogenates, and TNF-alpha in spleen homogenates were significantly decreased, whereas interleukin (IL)-10 in spleen homogenates was increased. Other cytokines (IL-2, IL-4, IL-6, IL-12p70 and monocyte chemotactic protein (MCP)-1) and myeloperoxidase (MPO) concentrations showed no differences. In conclusion, 16 days pretreatment with rosiglitazone impaired DSS-induced colitis in mice.
Ramakers
Julian D
JD
Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands. j.ramakers@hb.unimaas.nl
Verstege
Marleen I
MI
Thuijls
Geertje
G
Te Velde
Anje A
AA
Mensink
Ronald P
RP
Plat
Jogchum
J
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism*; D009195:Peroxidase / Q000097:blood; D010750:Phosphoproteins / Q000378:metabolism; D000077154:Rosiglitazone; D000683:Serum Amyloid P-Component / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology*; D062826:Zonula Occludens-1 Protein
D016207:Cytokines; D008565:Membrane Proteins; D047495:PPAR gamma; D010750:Phosphoproteins; D000683:Serum Amyloid P-Component; C569042:TJP1 protein, human; D045162:Thiazolidinediones; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D000077154:Rosiglitazone; D016264:Dextran Sulfate; D009195:Peroxidase