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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

Therapeutic effect of M2-BMDMs on DSS colitis.DSS was administered to mice to induce colitis and M0 or M2-BMDMs were transferred intravenously. (a) Relative body weight change, (b) disease activity index, and (c) colon length of mice with colitis, treated with M0 or M2 BMDMs or untreated (DSS), and control mice. (d) Histological appearance and histological scores of colons. (e) IL-1β, IL-6, and TNF-α in serum. (f) Quantitation of Arg1 protein expression in serial sections by immunohistochemistry. The mean IOD (IOD/total area) represents the Arg1 expression level. Data are representative of 6 mice/group, with similar staining. Data are shown as mean ± SD for three independent experiments, Comparisons between means used t tests (*P < 0.05, **P < 0.01, ***P < 0.001).
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f4: Therapeutic effect of M2-BMDMs on DSS colitis.DSS was administered to mice to induce colitis and M0 or M2-BMDMs were transferred intravenously. (a) Relative body weight change, (b) disease activity index, and (c) colon length of mice with colitis, treated with M0 or M2 BMDMs or untreated (DSS), and control mice. (d) Histological appearance and histological scores of colons. (e) IL-1β, IL-6, and TNF-α in serum. (f) Quantitation of Arg1 protein expression in serial sections by immunohistochemistry. The mean IOD (IOD/total area) represents the Arg1 expression level. Data are representative of 6 mice/group, with similar staining. Data are shown as mean ± SD for three independent experiments, Comparisons between means used t tests (*P < 0.05, **P < 0.01, ***P < 0.001).

Mentions: To further elucidate the importance of M2-BMDMs in IBD, we adoptively transferred M0- and M2-BMDMs into colitis-bearing recipient mice. There was no significant difference between the mice treated with M0-BMDMs and the colitis-only control group. In contrast, mice receiving M2-BMDMs showed significantly less weight loss compared with the colitis-only control group, with lowered DAI (Fig. 4a,b) and improved histological condition of the colon (Fig. 3c,d). Moreover, the M2-BMDM recipient mice possessed less IL-6, TNF-α, and IL-1β in the serum than the colitis-only control mice (Fig. 4e). Furthermore, increased Arg1 protein expression was detected in the colonic tissues of M2-BMDM recipient mice than in control tissues (Fig. 4f). These data demonstrated that M2 macrophage can protect against DSS-induced colitis in mice.


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)

Therapeutic effect of M2-BMDMs on DSS colitis.DSS was administered to mice to induce colitis and M0 or M2-BMDMs were transferred intravenously. (a) Relative body weight change, (b) disease activity index, and (c) colon length of mice with colitis, treated with M0 or M2 BMDMs or untreated (DSS), and control mice. (d) Histological appearance and histological scores of colons. (e) IL-1β, IL-6, and TNF-α in serum. (f) Quantitation of Arg1 protein expression in serial sections by immunohistochemistry. The mean IOD (IOD/total area) represents the Arg1 expression level. Data are representative of 6 mice/group, with similar staining. Data are shown as mean ± SD for three independent experiments, Comparisons between means used t tests (*P < 0.05, **P < 0.01, ***P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: Therapeutic effect of M2-BMDMs on DSS colitis.DSS was administered to mice to induce colitis and M0 or M2-BMDMs were transferred intravenously. (a) Relative body weight change, (b) disease activity index, and (c) colon length of mice with colitis, treated with M0 or M2 BMDMs or untreated (DSS), and control mice. (d) Histological appearance and histological scores of colons. (e) IL-1β, IL-6, and TNF-α in serum. (f) Quantitation of Arg1 protein expression in serial sections by immunohistochemistry. The mean IOD (IOD/total area) represents the Arg1 expression level. Data are representative of 6 mice/group, with similar staining. Data are shown as mean ± SD for three independent experiments, Comparisons between means used t tests (*P < 0.05, **P < 0.01, ***P < 0.001).
Mentions: To further elucidate the importance of M2-BMDMs in IBD, we adoptively transferred M0- and M2-BMDMs into colitis-bearing recipient mice. There was no significant difference between the mice treated with M0-BMDMs and the colitis-only control group. In contrast, mice receiving M2-BMDMs showed significantly less weight loss compared with the colitis-only control group, with lowered DAI (Fig. 4a,b) and improved histological condition of the colon (Fig. 3c,d). Moreover, the M2-BMDM recipient mice possessed less IL-6, TNF-α, and IL-1β in the serum than the colitis-only control mice (Fig. 4e). Furthermore, increased Arg1 protein expression was detected in the colonic tissues of M2-BMDM recipient mice than in control tissues (Fig. 4f). These data demonstrated that M2 macrophage can protect against DSS-induced colitis in mice.

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