title: PPARalpha activation abolishes LDL-stimulated IL-8 production via AP-1 deactivation in human aortic smooth muscle cells.
abstract: Native low density lipoprotein (n-LDL) is a major risk factor for cardiovascular diseases by inducing inflammatory processes and vascular smooth muscle cell proliferation in vessel cells. It has previously been reported that LDL enhances inflammatory reactions by the up-regulation of interleukin (IL)-8 via the activation of p38 kinase and activator protein (AP)-1 in human aortic smooth muscle cells (hAoSMCs). The findings of this study show, for the first time, that the peroxisome proliferator-activated receptor (PPARalpha) agonist, fenofibrate, completely abolishes the LDL-induced IL-8 up-regulation at the transcriptional level. Pretreatment of hAoSMCs with fenofibrate abolishes the effects of LDL on AP-1 activation without affecting nuclear factor (NF)-kappaB. In contrast, fenofibrate failed to modulate the activation state of p38 and JNK kinases or the levels of c-fos and phospho-Jun. These data suggest that AP-1 is likely to be located at the crossroads between LDL signaling and the regulation of IL-8 modulation by PPARalpha.
authors.affiliation: Genomic Research Center, Korea Research Institute of Bioscience and Biotechnology, Yusong, Daejeon, Republic of Korea.
authors.forename: Sungwoo
authors.initials: S
authors.lastname: Ryoo
authors.forename: Misun
authors.initials: M
authors.lastname: Won
authors.forename: Dong-Uk
authors.initials: DU
authors.lastname: Kim
authors.forename: Lila
authors.initials: L
authors.lastname: Kim
authors.forename: Gyoonhee
authors.initials: G
authors.lastname: Han
authors.forename: Seung-Kiel
authors.initials: SK
authors.lastname: Park
authors.forename: Naofumi
authors.initials: N
authors.lastname: Mukaida
authors.forename: Piljae
authors.initials: P
authors.lastname: Maeng
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Yoo
authors.forename: Kwang-Lae
authors.initials: KL
authors.lastname: Hoe
mesh_terms: D001011:Aorta / Q000166:cytology; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D011345:Fenofibrate / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D008156:Luciferases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D016209:Interleukin-8; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D018160:Receptors, Cytoplasmic and Nuclear; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D008156:Luciferases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D011345:Fenofibrate