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Updated: Feb 13, 2026

Polarization and Characterization of M1 and M2 Human Monocyte-Derived Macrophages on Implant Surfaces
Published on: December 6, 2024
Inhibitor of apoptosis proteins, NAIP, cIAP1 and cIAP2 expression during macrophage differentiation and M1/M2
Virginia Morón-Calvente1,2, Salvador Romero-Pinedo2,3, Sofía Toribio-Castelló2
1Department of Cell Biology, University of Granada, Granada, Spain.
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.
Insights
This study reveals how Inhibitor of Apoptosis (IAP) proteins, including NAIP, cIAP1, and cIAP2, change during macrophage polarization. These findings offer insights into immune cell regulation and potential therapeutic targets.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Monocytes and macrophages are crucial immune cells with plastic phenotypes (M1 and M2) for defense and repair.
- Inhibitor of Apoptosis (IAP) proteins regulate cellular processes, including immunity.
Purpose of the Study:
- To investigate the differential expression of NAIP, cIAP1, and cIAP2 during macrophage differentiation and polarization.
- To analyze the impact of the IAP antagonist SMC-LCL161 on IAP expression in polarized macrophages.
Main Methods:
- Analysis of NAIP, cIAP1, and cIAP2 expression in polarized THP-1 cells and primary human macrophages.
- Treatment of macrophages with the IAP antagonist SMC-LCL161.
Main Results:
- NAIP is highly expressed in M2 macrophages, while cIAP1 and cIAP2 show distinct expression patterns in M1 and M2 phenotypes.
- SMC-LCL161 treatment modulated NAIP, cIAP1, and cIAP2 expression, with NAIP upregulated in M2, cIAP1 downregulated in both M1/M2, and cIAP2 induced in M1.
Conclusions:
- IAP protein expression is differentially regulated during macrophage polarization.
- IAP antagonists can modulate macrophage polarization, suggesting potential therapeutic applications in immune modulation.
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