title: Troglitazone but not conjugated linoleic acid reduces gene expression and activity of matrix-metalloproteinases-2 and -9 in PMA-differentiated THP-1 macrophages.
abstract: Gene expression and activity of matrix-metalloproteinases (MMP)-2 and -9 in macrophages are reduced through peroxisome proliferator-activated receptor gamma (PPARgamma)-dependent inhibition of NF-kappaB. Since conjugated linoleic acids (CLAs) are PPARgamma ligands and known to inhibit NF-kappaB via PPARgamma, we studied whether CLA isomers are capable of reducing gene expression and gelatinolytic activity of MMP-2 and -9 in PMA-differentiated THP-1 macrophages, which has not yet been investigated. Incubation of PMA-differentiated THP-1 cells with either c9t11-CLA, t10c12-CLA or linoleic acid (LA), as a reference fatty acid, resulted in a significant incorporation of the respective fatty acids into total cell lipids relative to control cells (P<.05). Treatment of PMA-differentiated THP-1 cells with 10 and 20 micromol/L troglitazone but not with 10 or 100 micromol/L c9t11-CLA, t10c12-CLA or LA reduced relative mRNA concentrations and activity of MMP-2 and MMP-9 compared to control cells (P<.05). DNA-binding activity of NF-kappaB and PPARgamma and mRNA expression of the NF-kappaB target gene cPLA2 were not influenced by treatment with CLA. In contrast, treatment of PMA-differentiated THP-1 cells with troglitazone significantly increased transactivation of PPARgamma and decreased DNA-binding activity of NF-kappaB and relative mRNA concentration of cPLA2 relative to control cells (P<.05). In conclusion, the present study revealed that CLA isomers, in contrast to troglitazone, did not reduce gene expression and activity of MMP-2 and -9 in PMA-differentiated THP-1 macrophages, which is probably explained by the observation that CLA isomers neither activated PPARgamma nor reduced DNA-binding activity of NF-kappaB. This suggests that CLA isomers are ineffective in MMP-associated extracellular matrix degradation which is thought to contribute to the progression and rupture of advanced atherosclerotic plaques.
authors.affiliation: Institut für Agrar-und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhalden-Strasse 26, D-06108 Halle, Saale, Germany. robert.ringseis@landw.uni-halle.de
authors.forename: Robert
authors.initials: R
authors.lastname: Ringseis
authors.forename: Nadja
authors.initials: N
authors.lastname: Schulz
authors.forename: Daniela
authors.initials: D
authors.lastname: Saal
authors.forename: Klaus
authors.initials: K
authors.lastname: Eder
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D050356:Lipid Metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D000077288:Troglitazone
chemical_list: D002839:Chromans; D044243:Linoleic Acids, Conjugated; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000077288:Troglitazone; D013755:Tetradecanoylphorbol Acetate