Src polarizes anti-inflammatory M2 macrophage phenotype and function
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- 英文论文题名：Src polarizes anti-inflammatory M2 macrophage phenotype and function
- 论文作者：Hu Xiang ; Qin Kewei ; Zhang Hua ; Li Tianliang ; Han Chaofeng ; Cao Xuetao
- 英文论文作者：Hu Xiang ; Qin Kewei ; Zhang Hua ; Li Tianliang ; Han Chaofeng ; Cao Xuetao ; National Key Laboratory of Medical Molecular Biology & Department of Immunology ; Institute of Basic Medical Sciences ; Peking Union Medical College ; Chinese Academy of Medical Sciences ; National Key Laboratory of Medical Immunology & Institute of Immunology ; Second Military Medical University
- 年：2016
- 作者机构：National Key Laboratory of Medical Molecular Biology & Department of Immunology,Institute of Basic Medical Sciences,Peking Union Medical College,Chinese Academy of Medical Sciences;National Key Laboratory of Medical Immunology & Institute of Immunology,Second Military Medical University;
- 英文论文关键词：Src ; M1/M2 macrophage ; colitis ; Arg1 ; STAT6
- 会议召开时间：2016-11-04
- 会议录名称：第十一届全国免疫学学术大会摘要汇编
- 英文会议录名称：Abstracts of 2016 CSI Congress on Immunology
- 语种：英文
- 分类号：R574.62
- 学会代码：IGMD
- 会议名称：第十一届全国免疫学学术大会
- 会议地点：中国安徽合肥
- 主办单位：中国免疫学会
- 学会名称：中国免疫学会
- 页数：1
- 文件大小：380k
- 原文格式：D
- 会议级别：全国
摘要
Purpose: Ulcerative colitis, a major inflammatory bowel disease, is an idiopathic inflammatory disorder of the colonic mucosa, accompanied by an aberrant immune reaction to intestinal microflora. Macrophages are central mediators of intestinal immune homeostasis and inflammation. However, the regulation of different phenotypes of macrophages in colitis is poorly understood. Methods: We have administrated Src inhibitor(Dasatinib) in vivo in DSS-induced colitis to investigate the role of Src in regulation of macrophages in colitis. Src inhibitor pretreated BMDMs also have been induced to M1 or M2 macrophags in vitro. Results: Here we showed that Dasatinib treated mice were more susceptible to the DSS-induced colitis, with much more sever inflammation response, more i NOS expression and TNF-α production and at the same time less Arg1 expression and IL-10 production in the colon tissue. What's more, there were more M1 macrophages but less M2 macrophages in the total intestinal macrophages from the colon of the Dasatinib-treated mice after DSS feeding. Mechanistic studies showed that activated Src could inhibit the IFN-γ induced expression of i NOS in BMDM. To the opposite, activated Src could promote the expression of IL-4 induced Arg1 and YM1 expression in BMDM. Further research revealed that Src could positively regulate IL-4-induced activation of Akt and STAT6, which were reported to be necessary for the generation of M2 macrophage phenotype, especially Arg1 expression. However, only overexpression of STAT6 could rescue the inhibition on Arg1 expression by Src inhibitor. Src could associate with STAT6, indicating that Src could activate STAT6. Conclusion: In sum, our results provide the new mechanistic insight to the polarization of M1 and M2 macrophages. Src polarizes anti-inflammatory M2 macrophage phenotype and function through STAT6, indicating the importance of SrcSTAT6 cascade as the target for the design of anti-inflammatory drugs.
Purpose: Ulcerative colitis, a major inflammatory bowel disease, is an idiopathic inflammatory disorder of the colonic mucosa, accompanied by an aberrant immune reaction to intestinal microflora. Macrophages are central mediators of intestinal immune homeostasis and inflammation. However, the regulation of different phenotypes of macrophages in colitis is poorly understood. Methods: We have administrated Src inhibitor(Dasatinib) in vivo in DSS-induced colitis to investigate the role of Src in regulation of macrophages in colitis. Src inhibitor pretreated BMDMs also have been induced to M1 or M2 macrophags in vitro. Results: Here we showed that Dasatinib treated mice were more susceptible to the DSS-induced colitis, with much more sever inflammation response, more i NOS expression and TNF-α production and at the same time less Arg1 expression and IL-10 production in the colon tissue. What's more, there were more M1 macrophages but less M2 macrophages in the total intestinal macrophages from the colon of the Dasatinib-treated mice after DSS feeding. Mechanistic studies showed that activated Src could inhibit the IFN-γ induced expression of i NOS in BMDM. To the opposite, activated Src could promote the expression of IL-4 induced Arg1 and YM1 expression in BMDM. Further research revealed that Src could positively regulate IL-4-induced activation of Akt and STAT6, which were reported to be necessary for the generation of M2 macrophage phenotype, especially Arg1 expression. However, only overexpression of STAT6 could rescue the inhibition on Arg1 expression by Src inhibitor. Src could associate with STAT6, indicating that Src could activate STAT6. Conclusion: In sum, our results provide the new mechanistic insight to the polarization of M1 and M2 macrophages. Src polarizes anti-inflammatory M2 macrophage phenotype and function through STAT6, indicating the importance of SrcSTAT6 cascade as the target for the design of anti-inflammatory drugs.
Purpose: Ulcerative colitis, a major inflammatory bowel disease, is an idiopathic inflammatory disorder of the colonic mucosa, accompanied by an aberrant immune reaction to intestinal microflora. Macrophages are central mediators of intestinal immune homeostasis and inflammation. However, the regulation of different phenotypes of macrophages in colitis is poorly understood. Methods: We have administrated Src inhibitor(Dasatinib) in vivo in DSS-induced colitis to investigate the role of Src in regulation of macrophages in colitis. Src inhibitor pretreated BMDMs also have been induced to M1 or M2 macrophags in vitro. Results: Here we showed that Dasatinib treated mice were more susceptible to the DSS-induced colitis, with much more sever inflammation response, more i NOS expression and TNF-α production and at the same time less Arg1 expression and IL-10 production in the colon tissue. What's more, there were more M1 macrophages but less M2 macrophages in the total intestinal macrophages from the colon of the Dasatinib-treated mice after DSS feeding. Mechanistic studies showed that activated Src could inhibit the IFN-γ induced expression of i NOS in BMDM. To the opposite, activated Src could promote the expression of IL-4 induced Arg1 and YM1 expression in BMDM. Further research revealed that Src could positively regulate IL-4-induced activation of Akt and STAT6, which were reported to be necessary for the generation of M2 macrophage phenotype, especially Arg1 expression. However, only overexpression of STAT6 could rescue the inhibition on Arg1 expression by Src inhibitor. Src could associate with STAT6, indicating that Src could activate STAT6. Conclusion: In sum, our results provide the new mechanistic insight to the polarization of M1 and M2 macrophages. Src polarizes anti-inflammatory M2 macrophage phenotype and function through STAT6, indicating the importance of SrcSTAT6 cascade as the target for the design of anti-inflammatory drugs.
引文