A unique role for p53 in the regulation of M2 macrophage polarization

L Li, DSW Ng, W-C Mah, FF Almeida, SA Rahmat, VK Rao, SC Leow, F Laudisi, MT Peh, AM Goh, JSY Lim, GD Wright,A Mortellaro,R Taneja, F Ginhoux, CG Lee, PK Moore and DP Lane

Cell Death and Differentiation (2015) 22, 1081–1093

Speaker: Yi-Zhen Wu (吳宜臻)                            Time: 13:00~14:00, Nov, 04 2015

Commentator: Dr. Yao Chang (張堯 老師)        Place: Room 601

Abstract:

        M2-polarization macrophages perform immunoregulatory functions including defense against infection, promotion of angiogenesis and wound healing. In most type of tumors, the infiltrated macrophages were identified to be the M2-polarized macrophages, which provides an immuno-suppressive microenvironment supporting tumor growth. P53 is known to be a critical factor playing an important role in preventing oncogenesis. Hence the authors want to explore whether p53 can affect the polarization of M2 Macrophages. In this study, authors found that p53 activity is increased in M2-polarization macrophages by nutlin-3a. Nutlin-3a is able to destabilize the p53/MDM2 complex to enhance p53 activation and downregulate M2-related gene. P53 downregulates the expression of M2-related genes by directly binding to c-MYC promoter region. Moreover, authors show that p53 also regulates M2 polarization in peritoneal macrophages from IL4-challenged mice. LPS tolerance defined as the reduced capacity of a cell to respond to LPS activation after an initial exposure to LPS stimulus. In this study, authors reveal that endogenous p53 regulates M2 polarization during the period of LPS tolerance and the nutlin-3a retards the development of tolerance to LPS in mice. In conclusion, p53 is the first transcription factor reported to suppress M2 macrophages polarization. Authors proposed that manipulation of the p53 system provides an additional approach to study the molecular basis of macrophage plasticity and also a novel strategy by activating p53 to abolish M2 polarization.

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