title: JNK1 and JNK2 differently regulate IL-12 production in THP-1 macrophage cells.
abstract: Macrophages play a key role in initiating the innate responses to infection by secreting cytokines such as interleukin-12 (IL-12). This study defined the distinct regulation of lipopolysaccharide (LPS)-mediated IL-12 production by c-jun NH(2)-terminal kinase (JNK)1 and JNK2 isoforms in human macrophages. Knockdown of JNK1 and JNK2 by small interference RNA (siRNA) reduced and enhanced LPS-induced IL-12 p40 production in THP-1 macrophage cells, respectively. The simultaneous knockdown of JNK1 and JNK2 augmented LPS-induced IL-12 production as well as a specific JNK inhibitor. In addition, transfection of siRNA against phosphoinositide 3-kinase (PI3K) p110beta attenuated LPS-induced IL-12 production and JNK1 phosphorylation, while not affecting JNK2 phosphorylation. These findings indicate that JNK1- and JNK2-mediated signaling plays a positive and a negative role, respectively, in LPS-induced IL-12 production and PI3K p110beta controls LPS-induced JNK1 activation, not JNK2 activation, resulting in the positive regulation of IL-12 production in THP-1 macrophage cells.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Utsugi
authors.forename: Kunio
authors.initials: K
authors.lastname: Dobashi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ono
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hisada
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Koga
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Kawata
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Matsuzaki
authors.forename: Haruka
authors.initials: H
authors.lastname: Aoki
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kamide
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000873:Anthracenes / Q000494:pharmacology; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis*; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000502:physiology*; D048056:Mitogen-Activated Protein Kinase 9 / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D000873:Anthracenes; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; D007527:Isoenzymes; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; C432165:pyrazolanthrone; D019869:Phosphatidylinositol 3-Kinases; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8