title: Pro-inflammatory properties for thiazolidinediones.
abstract: 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.
authors.affiliation: Department of Physiology, Bât. B42, Molecular and Cellular Therapy Center, University of Liège, B-4000 Liège, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Desmet
authors.forename: Barbara
authors.initials: B
authors.lastname: Warzée
authors.forename: Philippe
authors.initials: P
authors.lastname: Gosset
authors.forename: Dorothée
authors.initials: D
authors.lastname: Mélotte
authors.forename: Anthony
authors.initials: A
authors.lastname: Rongvaux
authors.forename: Laurent
authors.initials: L
authors.lastname: Gillet
authors.forename: Laurence
authors.initials: L
authors.lastname: Fiévez
authors.forename: Grégory
authors.initials: G
authors.lastname: Seumois
authors.forename: Alain
authors.initials: A
authors.lastname: Vanderplasschen
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Pierre
authors.initials: P
authors.lastname: Lekeux
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
mesh_terms: 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
chemical_list: D002839:Chromans; D016207:Cytokines; D018836:Inflammation Mediators; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077288:Troglitazone