Limits...
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

Wound healing and cell migration in MLE-12 cell cultures.(a) Wounded MLE-12 cells were treated with supernatants conditioned for 24 h by non-polarized (M0) or M2-BMDMs cells in the absence (M2) or presence (+But) of butyrate. Photographs (×100) were taken at 0 and 12 h, after the wound was made. The extent of wound closure of MLE-12 was measured and expressed as a percentage. (b) Transwell filter assay was used to measure chemoattraction and migration of MLE-12 cells to lower wells containing conditioned media from non-polarized (M0) or M2-BMDM cells in the absence (M2) or presence (+But) of butyrate. Migrated cells at the lower surface of the transwell filter were stained with DAPI and counted. (c) Total RNA was isolated from M0-BMDMs, and M2-BMDMs, untreated or treated with butyrate, and analyzed by RT-PCR for the expression of representative M2 macrophage chemokine genes. 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

License
getmorefigures.php?uid=PMC4837405&req=5

f2: Wound healing and cell migration in MLE-12 cell cultures.(a) Wounded MLE-12 cells were treated with supernatants conditioned for 24 h by non-polarized (M0) or M2-BMDMs cells in the absence (M2) or presence (+But) of butyrate. Photographs (×100) were taken at 0 and 12 h, after the wound was made. The extent of wound closure of MLE-12 was measured and expressed as a percentage. (b) Transwell filter assay was used to measure chemoattraction and migration of MLE-12 cells to lower wells containing conditioned media from non-polarized (M0) or M2-BMDM cells in the absence (M2) or presence (+But) of butyrate. Migrated cells at the lower surface of the transwell filter were stained with DAPI and counted. (c) Total RNA was isolated from M0-BMDMs, and M2-BMDMs, untreated or treated with butyrate, and analyzed by RT-PCR for the expression of representative M2 macrophage chemokine genes. 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: M2 macrophage promotes the resolution of wound healing by facillating cell migration to damaged tissues1415. To analyze if butyrate influences M2 macrophage function, wound-healing assay was performed using MLE-12 bronchial cells in an in vitro scrape model. As shown in Fig. 2a, supernatants from M2-BMDMs increased wound closure compared with those from the M0-BMDMs (p < 0.05) and this effect on re-epithelialization was improved further when M2-BMDMs had been treated with butyrate. As shown in Fig. 2b, medium conditioned by M2-BMDMs for 24 h promoted the migration of MLE-12 cells in transwell filter assays. The number of MLE-12 cells in the permeating septum after 12 h more than doubled (p < 0.05) in the presence of medium conditioned by M2-BMDMs rather than M0 and doubled again (p < 0.01) when conditioning had occurred in the presence of butyrate. Together, these data demonstrated that butyrate significantly enhanced the functional ability of M2-BMDMs promote cell migration and wound-healing. Consistent with this, the expression of relevant C-C cytokine genes, CCL2, CCL17, and CCL22 was consistently higher in butyrate-treated M2-BMDMs (Fig. 2c).


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)

Wound healing and cell migration in MLE-12 cell cultures.(a) Wounded MLE-12 cells were treated with supernatants conditioned for 24 h by non-polarized (M0) or M2-BMDMs cells in the absence (M2) or presence (+But) of butyrate. Photographs (×100) were taken at 0 and 12 h, after the wound was made. The extent of wound closure of MLE-12 was measured and expressed as a percentage. (b) Transwell filter assay was used to measure chemoattraction and migration of MLE-12 cells to lower wells containing conditioned media from non-polarized (M0) or M2-BMDM cells in the absence (M2) or presence (+But) of butyrate. Migrated cells at the lower surface of the transwell filter were stained with DAPI and counted. (c) Total RNA was isolated from M0-BMDMs, and M2-BMDMs, untreated or treated with butyrate, and analyzed by RT-PCR for the expression of representative M2 macrophage chemokine genes. 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

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

f2: Wound healing and cell migration in MLE-12 cell cultures.(a) Wounded MLE-12 cells were treated with supernatants conditioned for 24 h by non-polarized (M0) or M2-BMDMs cells in the absence (M2) or presence (+But) of butyrate. Photographs (×100) were taken at 0 and 12 h, after the wound was made. The extent of wound closure of MLE-12 was measured and expressed as a percentage. (b) Transwell filter assay was used to measure chemoattraction and migration of MLE-12 cells to lower wells containing conditioned media from non-polarized (M0) or M2-BMDM cells in the absence (M2) or presence (+But) of butyrate. Migrated cells at the lower surface of the transwell filter were stained with DAPI and counted. (c) Total RNA was isolated from M0-BMDMs, and M2-BMDMs, untreated or treated with butyrate, and analyzed by RT-PCR for the expression of representative M2 macrophage chemokine genes. 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: M2 macrophage promotes the resolution of wound healing by facillating cell migration to damaged tissues1415. To analyze if butyrate influences M2 macrophage function, wound-healing assay was performed using MLE-12 bronchial cells in an in vitro scrape model. As shown in Fig. 2a, supernatants from M2-BMDMs increased wound closure compared with those from the M0-BMDMs (p < 0.05) and this effect on re-epithelialization was improved further when M2-BMDMs had been treated with butyrate. As shown in Fig. 2b, medium conditioned by M2-BMDMs for 24 h promoted the migration of MLE-12 cells in transwell filter assays. The number of MLE-12 cells in the permeating septum after 12 h more than doubled (p < 0.05) in the presence of medium conditioned by M2-BMDMs rather than M0 and doubled again (p < 0.01) when conditioning had occurred in the presence of butyrate. Together, these data demonstrated that butyrate significantly enhanced the functional ability of M2-BMDMs promote cell migration and wound-healing. Consistent with this, the expression of relevant C-C cytokine genes, CCL2, CCL17, and CCL22 was consistently higher in butyrate-treated M2-BMDMs (Fig. 2c).

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