Inhibitor of apoptosis proteins, NAIP, cIAP1 and cIAP2 expression during macrophage differentiation and M1/M2 polarization.

Virginia Morón-Calvente,Eric C Lacasse,Shawn T Beug,Alex Mackenzie,Salvador Romero-Pinedo,Robert Korneluk,Sofía Toribio-Castelló,Domingo I Rojas-Barros,Ana C Abadía-Molina,Julio Plaza-Díaz,Francisco Abadía-Molina

doi:10.1371/journal.pone.0193643

Abstract

Monocytes and macrophages constitute the first line of defense of the immune system against external pathogens. Macrophages have a highly plastic phenotype depending on environmental conditions; the extremes of this phenotypic spectrum are a pro-inflammatory defensive role (M1 phenotype) and an anti-inflammatory tissue-repair one (M2 phenotype). The Inhibitor of Apoptosis (IAP) proteins have important roles in the regulation of several cellular processes, including innate and adaptive immunity. In this study we have analyzed the differential expression of the IAPs, NAIP, cIAP1 and cIAP2, during macrophage differentiation and polarization into M1 or M2. In polarized THP-1 cells and primary human macrophages, NAIP is abundantly expressed in M2 macrophages, while cIAP1 and cIAP2 show an inverse pattern of expression in polarized macrophages, with elevated expression levels of cIAP1 in M2 and cIAP2 preferentially expressed in M1. Interestingly, treatment with the IAP antagonist SMC-LCL161, induced the upregulation of NAIP in M2, the downregulation of cIAP1 in M1 and M2 and an induction of cIAP2 in M1 macrophages.

Highlights

The innate immune system is the first line of defense against external pathogens
NAIP between monocytes and M0 or polarized macrophages (P = 0.363, Fig 3B), we observed a significant increase of NAIP levels in M2 macrophages by immunofluorescence (Fig 3C and 3D); with respect to NAIP expression in polarized macrophages we want to emphasized that, lower NAIP expression in M1 cells with greater NAIP levels in the M2 state are shown both in THP-1 and Peripheral blood mononuclear cells (PBMCs) derived M1/M2 macrophages with a good correlation in NAIP mRNA and protein levels by western blot (Figs 2 and 3A and 3B)
We found that the cellular IAP 1 (cIAP1) protein expression level was significantly increased following PMA-induced differentiation of monocytes into M0 and that that level of expression was maintained in M2 macrophages (Fig 4A and 4B)

Summary

Introduction

The innate immune system is the first line of defense against external pathogens. The innate immunity response to pathogens is nonspecific and largely depends on macrophages. Macrophages are a heterogeneous cell population that participates in tissue homeostasis, including the removal of apoptotic cells and cellular debris and in tissue remodelling and repair [1, 2]. Due to their multifunctional roles, macrophages are highly plastic and can modify their. IAPs expression in macrophage differentiation and polarization. Institutes of Health Research;#231421, #318176, #361847: STB, ECL, RK The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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