title: Enhancement of inflammatory protein expression and nuclear factor Κb (NF-Κb) activity by trichostatin A (TSA) in OP9 preadipocytes.
abstract: The production of inflammatory proteins such as interleukin-6 (IL-6) by preadipocytes and mature adipocytes is closely associated with the impairment of systemic glucose homeostasis. However, precisely how the production is regulated and the roles of histone deacetylases (HDACs) remain largely unknown. The aim of this study was to establish whether HDAC inhibitors affect the expression of inflammatory proteins in pre/mature adipocytes, and, if so, to determine the mechanism involved. Trichostatin A (TSA), an HDAC inhibitor, enhanced lipopolysaccharide (LPS)-induced production of IL-6 in OP9 preadipocytes but not the mature adipocytes. Moreover, TSA also enhanced palmitic acid-induced IL-6 production and the expression of inflammatory genes induced by LPS in preadipocytes. Although TSA did not affect TLR4 mRNA expression or the activation of MAPKs, a reporter gene assay revealed that the LPS-induced increase in nuclear factor κB (NF-κB) activity was enhanced by TSA. Moreover, TSA increased the level of NF-κB p65 acetylation at lysine 310 and duration of its translocation into the nucleus, which leads to enhancement of NF-κB activity and subsequently expression of inflammatory genes. These findings shed new light on the regulatory roles of HDACs in preadipocytes in the production of inflammatory proteins.
authors.affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Sato
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kotake
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiratsuka
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D018932:Chemokine CCL2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006706:Homeostasis; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D051379:Mice; D019308:Palmitic Acid / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D015850:Interleukin-6; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D019308:Palmitic Acid; C012589:trichostatin A; D006655:Histone Deacetylases; D005947:Glucose; D008239:Lysine
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