title: Conjugated linoleic acid regulates phosphorylation of PPARγ by modulation of ERK 1/2 and p38 signaling in human macrophages/fatty acid-laden macrophages.
abstract: Stimulation of macrophages by a variety fatty acids causes activation of MAP kinases (MAPKs). The consequences arising from down-regulation of MAPKs may be a limitation in the activity of PPARγ, which is modulated by a modification catalyzed by these kinases. Phosphorylation of MAP kinases-ERK1/2 and p38 as well as PPARγ was determined by real-time polymerase chain reaction and Western blotting in human macrophages cultured with conjugated linoleic acids (CLAs). We demonstrated that CLA isomers alter MAP kinase phosphorylation and PPARγ activation. Phosphorylation of ERK1/2 was diminished in cells cultivated with cis-9,trans-11 CLA, whereas phosphorylation of p38 was reduced by trans-10,cis-12 CLA. PPARγ was phosphorylated mainly by ERK1/2, and consequently, PPARγ phosphorylation was suppressed mainly by cis-9,trans-11 isomer. In human adipocytes, cis-9,trans-11 C 18:2 raised the activation of PPAR and several of its downstream target genes. We suggest that a similar process may also occur in human macrophages.
authors.affiliation: Department of Biochemistry and Human Nutrition, Pomeranian Medical University, Szczecin, Poland. ewa.stachowska@pum.edu.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Stachowska
authors.forename: Jacek
authors.initials: J
authors.lastname: Kijowski
authors.forename: Violetta
authors.initials: V
authors.lastname: Dziedziejko
authors.forename: Aldona
authors.initials: A
authors.lastname: Siennicka
authors.forename: Dariusz
authors.initials: D
authors.lastname: Chlubek
mesh_terms: D002460:Cell Line; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000201:enzymology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D044243:Linoleic Acids, Conjugated; D047495:PPAR gamma; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases