title: Aurora kinase a regulates m1 macrophage polarization and plays a role in experimental autoimmune encephalomyelitis.
abstract: Macrophage polarization is a dynamic and integral process of tissue inflammation and remodeling. Here we demonstrate an important role of Aurora kinase A in the regulation of inflammatory M1 macrophage polarization. We found that there was an elevated expression of Aurora-A in M1 macrophages and inhibition of Aurora-A by small molecules or specific siRNA selectively led to the suppression of M1 polarization, sparing over the M2 macrophage differentiation. At the molecular level, we found that the effects of Aurora-A in M1 macrophages were mediated through the down-regulation of NF-κB pathway and subsequent IRF5 expression. In an autoimmune disease model, experimental autoimmune encephalitis (EAE), treatment with Aurora kinase inhibitor blocked the disease development and shifted the macrophage phenotype from inflammatory M1 to anti-inflammatory M2. Thus, this study reveals a novel function of Aurora-A in controlling the polarization of macrophages, and modification of Aurora-A activity may lead to a new therapeutic approach for chronic inflammatory diseases.
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Ding
authors.forename: Haijuan
authors.initials: H
authors.lastname: Gu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Gao
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
authors.forename: Biao
authors.initials: B
authors.lastname: Zheng
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines
chemical_list: D064096:Aurora Kinase A; D010879:Piperazines; D047428:Protein Kinase Inhibitors; C484810:tozasertib; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines