Pro-inflammatory properties for thiazolidinediones.
Thiazolidinediones (TZDs) are pharmacological ligands of the peroxisome proliferator-activated receptor (PPAR)-gamma that are extensively used in the treatment of type II diabetes. Recently, an anti-inflammatory potential for TZDs has been suggested, based on observations that these compounds may inhibit pro-inflammatory cytokine expression in vitro and may attenuate the inflammatory response in vivo. Here, we show that the TZDs rosiglitazone (RSG) and troglitazone (TRO) do not inhibit the inflammatory response to tumor necrosis factor (TNF)-alpha in various epithelial cell types. On the contrary, both RSG and TRO significantly potentiated TNF-alpha-induced production of granulocyte/macrophage-colony-stimulating factor, interleukin (IL)-6 and/or IL-8 in these cells. This increase in pro-inflammatory cytokine expression was functionally significant as supernatants from cells co-treated with TNF-alpha and TZDs displayed increased neutrophil pro-survival activity when compared with supernatants from cells treated with TNF-alpha alone. Additionally, it was shown that TZDs enhance cytokine expression at the transcriptional level, but that the pro-inflammatory effects of TZDs are independent on PPARgamma, nuclear factor kappaB or mitogen-activated protein kinase activation. Our study shows that TZDs may potentiate the inflammatory response in epithelial cells, a previously unappreciated effect of these compounds.
Desmet
Christophe
C
Department of Physiology, Bât. B42, Molecular and Cellular Therapy Center, University of Liège, B-4000 Liège, Belgium.
Warzée
Barbara
B
Gosset
Philippe
P
Mélotte
Dorothée
D
Rongvaux
Anthony
A
Gillet
Laurent
L
Fiévez
Laurence
L
Seumois
Grégory
G
Vanderplasschen
Alain
A
Staels
Bart
B
Lekeux
Pierre
P
Bureau
Fabrice
F
D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002839:Chromans / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology / Q000633:toxicity*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology / Q000633:toxicity*; D000077288:Troglitazone
D002839:Chromans; D016207:Cytokines; D018836:Inflammation Mediators; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077288:Troglitazone