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Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

Ji J, Shu D, Zheng M, Wang J, Luo C, Wang Y, Guo F, Zou X, Lv X, Li Y, Liu T, Qu H - Sci Rep (2016)

Bottom Line: Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells.Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1.Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.

ABSTRACT
Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

No MeSH data available.


Related in: MedlinePlus

Butyrate increases acetylation of H3K9.(a) M2-BMDMs cultured in the presence of butyrate for 6 h were examined for expression of HDAC 1, 2, 3, 6, 7, and 9 by quantitative RT-PCR. Data are the mean ± SD of three independent experiments. (b) M2-BMDMs were treated with butyrate for 12 h. The level of H3K9 acetylation were assessed by immunoblot. Total histone and β-actin levels were used as loading controls. Data are representative of three independent experiments.
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f6: Butyrate increases acetylation of H3K9.(a) M2-BMDMs cultured in the presence of butyrate for 6 h were examined for expression of HDAC 1, 2, 3, 6, 7, and 9 by quantitative RT-PCR. Data are the mean ± SD of three independent experiments. (b) M2-BMDMs were treated with butyrate for 12 h. The level of H3K9 acetylation were assessed by immunoblot. Total histone and β-actin levels were used as loading controls. Data are representative of three independent experiments.

Mentions: Butyrate, as a histone deacetylase (HDAC) inhibitor, is known to regulate gene expression epigenetically2223. Whether butyrate alters the histone acetylation of BMDMs to epigenetically regulate the transcription of genes responsible for M2-BMDM development or function is still unknown. We hypothesized that butyrate enhanced the polarization of M2 macrophage involved the HDACs inhibition. To test this hypothesis, M2-BMDMs were stimulated with butyrate for 6 h and the expression of HDAC genes was analyzed. The expression of HDAC1, HDAC6, HDAC7, and HDAC9 was reduced in M2-BMDMs, while no differences were observed in HDAC2 and HDAC3 gene expression. Butyrate-treated M2-BMDMs had lower HDAC1 gene expression than M2-BMDMs (Fig. 6a). Western blot analysis demonstrated that butyrate treatment of M2-BMDMs enhanced histone 3 lysine 9 acetylation (H3K9) (Fig. 6b). These results suggested that butyrate enhanced M2-BMDMs polarization partly through HDAC1 inhibition and histone H3K9 acetylation.


Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

Ji J, Shu D, Zheng M, Wang J, Luo C, Wang Y, Guo F, Zou X, Lv X, Li Y, Liu T, Qu H - Sci Rep (2016)

Butyrate increases acetylation of H3K9.(a) M2-BMDMs cultured in the presence of butyrate for 6 h were examined for expression of HDAC 1, 2, 3, 6, 7, and 9 by quantitative RT-PCR. Data are the mean ± SD of three independent experiments. (b) M2-BMDMs were treated with butyrate for 12 h. The level of H3K9 acetylation were assessed by immunoblot. Total histone and β-actin levels were used as loading controls. Data are representative of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837405&req=5

f6: Butyrate increases acetylation of H3K9.(a) M2-BMDMs cultured in the presence of butyrate for 6 h were examined for expression of HDAC 1, 2, 3, 6, 7, and 9 by quantitative RT-PCR. Data are the mean ± SD of three independent experiments. (b) M2-BMDMs were treated with butyrate for 12 h. The level of H3K9 acetylation were assessed by immunoblot. Total histone and β-actin levels were used as loading controls. Data are representative of three independent experiments.
Mentions: Butyrate, as a histone deacetylase (HDAC) inhibitor, is known to regulate gene expression epigenetically2223. Whether butyrate alters the histone acetylation of BMDMs to epigenetically regulate the transcription of genes responsible for M2-BMDM development or function is still unknown. We hypothesized that butyrate enhanced the polarization of M2 macrophage involved the HDACs inhibition. To test this hypothesis, M2-BMDMs were stimulated with butyrate for 6 h and the expression of HDAC genes was analyzed. The expression of HDAC1, HDAC6, HDAC7, and HDAC9 was reduced in M2-BMDMs, while no differences were observed in HDAC2 and HDAC3 gene expression. Butyrate-treated M2-BMDMs had lower HDAC1 gene expression than M2-BMDMs (Fig. 6a). Western blot analysis demonstrated that butyrate treatment of M2-BMDMs enhanced histone 3 lysine 9 acetylation (H3K9) (Fig. 6b). These results suggested that butyrate enhanced M2-BMDMs polarization partly through HDAC1 inhibition and histone H3K9 acetylation.

Bottom Line: Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells.Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1.Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

View Article: PubMed Central - PubMed

Affiliation: Institute of Animal Science, Guangdong Academy of Agricultural Sciences, 1 Dafeng 1st Street, Wushan, Tianhe District, Guangzhou 510640, China.

ABSTRACT
Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

No MeSH data available.


Related in: MedlinePlus