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NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization.

Liu Q, Tian Y, Zhao X, Jing H, Xie Q, Li P, Li D, Yan D, Zhu X - Mol. Cells (2015)

Bottom Line: Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization.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-N1), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1N2), 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-N2) 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

ABSTRACT
Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-GuC)rin) activates disabled naC/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-N1), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1N2), 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-N2) 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.

No MeSH data available.


Related in: MedlinePlus

NMAAP1 expression was associated with the percent of M1 macrophages in BCG-activated peritoneal macrophages. (A) The percent of M1 macrophages in peritoneal macrophages on day 4, day 8 and day 12 were assessed using FACS. (B) Linear graphs analysis of the percent of M1 macrophages in BCG-activated macrophage. (C) IL-10 and NMAAP1 expression after BCG stimulation on day 4, day 8 and day 12 was determined using quantitative RT-PCR (qPCR). (D) Determination of IL-10 and TNF-α release using ELISA in BCG-stimulated mice sera after day 4, day 8 and day 12. Data are represented as mean ± S.E.M. from at least three independent experiments.
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f1-molce-38-10-886: NMAAP1 expression was associated with the percent of M1 macrophages in BCG-activated peritoneal macrophages. (A) The percent of M1 macrophages in peritoneal macrophages on day 4, day 8 and day 12 were assessed using FACS. (B) Linear graphs analysis of the percent of M1 macrophages in BCG-activated macrophage. (C) IL-10 and NMAAP1 expression after BCG stimulation on day 4, day 8 and day 12 was determined using quantitative RT-PCR (qPCR). (D) Determination of IL-10 and TNF-α release using ELISA in BCG-stimulated mice sera after day 4, day 8 and day 12. Data are represented as mean ± S.E.M. from at least three independent experiments.

Mentions: We examined the phenotype of BCG-activated macrophages to delineate the effect of BCG on macrophage biological functions. We detected the expression of M1 and M2 cell markers and NMAAP1 levels. CD16/32 (M1) and CD23 (M2) were used to detect the phenotypes of BCG-activated macrophages. The percentage of BCG-activated macrophages that expressed M1 markers increased on day 4 and decreased on day 8. Mice were challenged with i.p. BCG on day 10. Therefore, there was an increase in these markers on day 12 (Figs. 1A and 1B).


NMAAP1 Expressed in BCG-Activated Macrophage Promotes M1 Macrophage Polarization.

Liu Q, Tian Y, Zhao X, Jing H, Xie Q, Li P, Li D, Yan D, Zhu X - Mol. Cells (2015)

NMAAP1 expression was associated with the percent of M1 macrophages in BCG-activated peritoneal macrophages. (A) The percent of M1 macrophages in peritoneal macrophages on day 4, day 8 and day 12 were assessed using FACS. (B) Linear graphs analysis of the percent of M1 macrophages in BCG-activated macrophage. (C) IL-10 and NMAAP1 expression after BCG stimulation on day 4, day 8 and day 12 was determined using quantitative RT-PCR (qPCR). (D) Determination of IL-10 and TNF-α release using ELISA in BCG-stimulated mice sera after day 4, day 8 and day 12. Data are represented as mean ± S.E.M. from at least three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4625070&req=5

f1-molce-38-10-886: NMAAP1 expression was associated with the percent of M1 macrophages in BCG-activated peritoneal macrophages. (A) The percent of M1 macrophages in peritoneal macrophages on day 4, day 8 and day 12 were assessed using FACS. (B) Linear graphs analysis of the percent of M1 macrophages in BCG-activated macrophage. (C) IL-10 and NMAAP1 expression after BCG stimulation on day 4, day 8 and day 12 was determined using quantitative RT-PCR (qPCR). (D) Determination of IL-10 and TNF-α release using ELISA in BCG-stimulated mice sera after day 4, day 8 and day 12. Data are represented as mean ± S.E.M. from at least three independent experiments.
Mentions: We examined the phenotype of BCG-activated macrophages to delineate the effect of BCG on macrophage biological functions. We detected the expression of M1 and M2 cell markers and NMAAP1 levels. CD16/32 (M1) and CD23 (M2) were used to detect the phenotypes of BCG-activated macrophages. The percentage of BCG-activated macrophages that expressed M1 markers increased on day 4 and decreased on day 8. Mice were challenged with i.p. BCG on day 10. Therefore, there was an increase in these markers on day 12 (Figs. 1A and 1B).

Bottom Line: Various transcription factors and signaling pathways are involved in the regulation of macrophage activation and polarization.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-N1), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1N2), 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-N2) 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

ABSTRACT
Macrophages are divided into two subpopulations: classically activated macrophages (M1) and alternatively activated macrophages (M2). BCG (Bacilli Calmette-GuC)rin) activates disabled naC/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-N1), Interleukin 6 (IL-6), Interleukin 12 (IL-12), Monocyte chemoattractant protein-1 (MCP-1) and Interleukin-1 beta (IL-1N2), 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-N2) 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.

No MeSH data available.


Related in: MedlinePlus