title: HDAC6 deacetylase activity is critical for lipopolysaccharide-induced activation of macrophages.
abstract: Activated macrophages play an important role in both innate and adaptive immune responses, and aberrant activation of macrophages often leads to inflammatory and immune disorders. However, the molecular mechanisms of how macrophages are activated are not fully understood. In this study, we identify a novel role for histone deacetylse 6 (HDAC6) in lipopolysaccharide (LPS)-induced macrophage activation. Our data show that suppression of HDAC6 activity significantly restrains LPS-induced activation of macrophages and production of pro-inflammatory cytokines. Further study reveals that the regulation of macrophage activation by HDAC6 is independent of F-actin polymerization and filopodium formation; instead, it is mediated by the effects of HDAC6 on cell adhesion and microtubule acetylation. These data thus suggest that HDAC6 is an important regulator of LPS-induced macrophage activation and might be a potential target for the management of inflammatory disorders.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Songbo
authors.initials: S
authors.lastname: Xie
authors.affiliation: Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ran
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Immune Microenvironment and Disease of the Ministry of Education, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D000199:Actins / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage; D006655:Histone Deacetylases / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects* / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008870:Microtubules / Q000276:immunology / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000199:Actins; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D008070:Lipopolysaccharides; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases