NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization

• Published in: Molecules and cells Vol. 38; no. 10; pp. 886 - 894
• Main Authors: Liu, Q., Jilin University, Changchun, China, Tian, Y., Jilin University, Changchun, China, Zhao, X., Guilin Medical University, Guilin, China, Jing, H., Jilin University, Changchun, China, Xie, Q., Jilin University, Changchun, China, Li, P., Jilin University, Changchun, China, Li, D., Jilin University, Changchun, China, Yan, D., Jilin University, Changchun, China, Zhu, X., Jilin University, Changchun, China
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.10.2015; 한국분자세포생물학회
• Subjects: Animals; Cell Line, Tumor; Chemokine CCL2 - metabolism; Cytotoxicity, Immunologic; differentiation,M1, NMAAP1,tumor; Interleukins - metabolism; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors - metabolism; MACROFAGOS; MACROPHAGE; Macrophage Activation; MACROPHAGES; Macrophages - immunology; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred ICR; Mycobacterium bovis - immunology; Neoplasms - immunology; Nitric Oxide Synthase Type II - metabolism; Phagocytosis; RAW 264.7 Cells; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling Proteins - metabolism; Tumor Necrosis Factor-alpha - metabolism; 생물학; macrophage; differentiation; M1; NMAAP1; tumor
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2015.0125

Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-Gu - rin) activates disabled na - ve macrophages to M1 macrophages, which act as inflammatory, microbicidal and tumoricidal cells through cell-cell contact and/or the release of soluble factors. Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization. We discovered that BCG-activated macrophages (BAM) expressed a new molecule, and we named it Novel Macrophage Activated Associated Protein 1 (NMAAP1). The current study found that the overexpression of NMAAP1 in macrophages results in M1 polarization with increased expression levels of M1 genes, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1beta), and decreased expression of some M2 genes, such as Kruppel-like factor 4 (KLF4) and suppressor of cytokine signaling 1 (SOCS1), but not other M2 genes, including arginase-1 (Arg-1), Interleukin (IL-10), transforming growth factor beta (TGF-beta) and found in inflammatory zone 1 (Fizz1). Moreover, NMAAP1 overexpression in the RAW264.7 cell line increased cytotoxicity against MCA207 tumor cells, which depends on increased inflammatory cytokines rather than cell-cell contact. NMAAP1 also substantially enhanced the phagocytic ability of macrophages, which implies that NMAAP1 promoted macrophage adhesive and clearance activities. Our results indicate that NMAAP1 is an essential molecule that modulates macrophages phenotype and plays an important role in macrophage tumoricidal functions.