title: Peptidoglycan induced expression of peroxisome proliferator-activated receptor γ in mouse peritoneal macrophages: role of ERK and JNK MAP kinases.
abstract: The peroxisome proliferator-activated receptor (PPAR) γ plays an important role in macrophage inflammatory homeostasis. Here we investigate the cross talk between PPARγ and TLR2 signaling pathway in mouse peritoneal macrophages. Real time RT-PCR and immunoblot analysis revealed that peptidoglycan (PGN) treatment of macrophages leads to biphasic effect on PPARγ expression i.e. an early upregulation and a late suppression. Inhibition of ERK MAP kinase by PD98059 abolished the early and rapid induction of PPARγ, while the inhibition of JNK MAP kinase by SP600125 nullifies the late inhibitory effect on the PPARγ expression in a dose-dependent manner. Furthermore, PPARγ knockdown macrophages showed enhanced NF-κB activity after PGN treatment. PGN treatment also enhances PPARγ interaction with p65 as observed by immunoprecipitation. This interaction may inhibit NF-κB (p65) activity as increased nuclear localization of p65 was observed in PPARγ knockdown macrophages after PGN treatment. PPARγ knockdown also increased the PGN-induced inflammatory cytokines (TNF-α, IL-1β, IL-12p40) production. Thus, our observations suggest that PGN induces PPARγ expression which is regulated by MAPKs activation and this enhanced PPARγ in turn attenuate NF-κB activity probably via enhancing p65 nuclear export. These results provide insight into how these pathways could be modulated in inflammatory diseases.
authors.affiliation: School of Biotechnology, Faculty of Science, Banaras Hindu University, Varanasi 221 005, India.
authors.forename: Kunal H
authors.initials: KH
authors.lastname: Bhatt
authors.forename: Ajit
authors.initials: A
authors.lastname: Sodhi
authors.forename: Rituparna
authors.initials: R
authors.lastname: Chakraborty
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002478:Cells, Cultured; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010457:Peptidoglycan / Q000276:immunology*; D034622:RNA Interference; D034741:RNA, Small Interfering; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000873:Anthracenes; D005419:Flavonoids; D053762:Interleukin-12 Subunit p40; D053583:Interleukin-1beta; D016328:NF-kappa B; D047495:PPAR gamma; D010457:Peptidoglycan; D034741:RNA, Small Interfering; C498144:Rela protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one