PMID- 30176559
OWN - NLM
STAT- MEDLINE
DCOM- 20191115
LR  - 20191115
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 111
DP  - 2018 Nov
TI  - Src promotes anti-inflammatory (M2) macrophage generation via the IL-4/STAT6 
      pathway.
PG  - 209-215
LID - S1043-4666(18)30366-1 [pii]
LID - 10.1016/j.cyto.2018.08.030 [doi]
AB  - The balance between pro-inflammatory and anti-inflammatory macrophage generation, 
      a process known as polarization, is critical for immune homoeostasis. Identifying 
      the molecular mechanisms underlying polarization and the generation of 
      anti-inflammatory macrophages is an area of high current interest. Our previous 
      work has demonstrated that integrin CD11b promotes IL-10 production in 
      macrophages by activating the Sarcoma gene (Src), yet whether and how Src 
      modulates anti-inflammatory macrophages is not known. Here we show that Src 
      inhibitor (Dasatinib)-treated mice were highly susceptible to dextran sulfate 
      sodium (DSS)-induced colitis, with a much more sever inflammation response, 
      accompanying by high TNF-alpha, and low IL-10 expression. Inhibition of Src enhanced 
      the expression of pro-inflammatory macrophage marker inducible nitric oxide 
      synthase (iNOS), but reduced the expression of anti-inflammatory macrophage 
      marker arginase1 (Arg1) in both intestinal macrophages and bone marrow-derived 
      macrophages (BMDMs). Overexpression of constitutively activated Src promoted 
      IL-4-induced expression of Arg1 through STAT6 phosphorylation, and Jak1 was also 
      involved in this process. Our results reveal that the IL-4-Src-STAT6 pathway 
      plays a major role in polarizing anti-inflammatory macrophage generation and 
      suggest a potential anti-inflammatory role for Src in inflammatory diseases.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Hu, Xiang
AU  - Hu X
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, 
      China.
FAU - Wang, Huamin
AU  - Wang H
AD  - Department of Immunology & Center for Immunotherapy, Institute of Basic Medical 
      Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, 
      Beijing 100005, China.
FAU - Han, Chaofeng
AU  - Han C
AD  - National Key Laboratory of Medical Immunology & Institute of Immunology, Second 
      Military Medical University, Shanghai 200433, China.
FAU - Cao, Xuetao
AU  - Cao X
AD  - Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, 
      China; Department of Immunology & Center for Immunotherapy, Institute of Basic 
      Medical Sciences, Peking Union Medical College, Chinese Academy of Medical 
      Sciences, Beijing 100005, China; National Key Laboratory of Medical Immunology & 
      Institute of Immunology, Second Military Medical University, Shanghai 200433, 
      China. Electronic address: caoxt@immunol.org.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180831
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 130068-27-8 (Interleukin-10)
RN  - 207137-56-2 (Interleukin-4)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 2.7.10.2 (Proto-Oncogene Proteins pp60(c-src))
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*metabolism
MH  - Cell Line
MH  - Colitis/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Interleukin-10/metabolism
MH  - Interleukin-4/*metabolism
MH  - Janus Kinase 1/metabolism
MH  - Macrophages/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Proto-Oncogene Proteins pp60(c-src)/*metabolism
MH  - RAW 264.7 Cells
MH  - STAT6 Transcription Factor/*metabolism
MH  - Signal Transduction/physiology
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - Inflammation
OT  - Macrophage polarization
OT  - STAT6
OT  - Src
EDAT- 2018/09/04 06:00
MHDA- 2019/11/16 06:00
CRDT- 2018/09/04 06:00
PHST- 2018/06/08 00:00 [received]
PHST- 2018/08/19 00:00 [revised]
PHST- 2018/08/28 00:00 [accepted]
PHST- 2018/09/04 06:00 [pubmed]
PHST- 2019/11/16 06:00 [medline]
PHST- 2018/09/04 06:00 [entrez]
AID - S1043-4666(18)30366-1 [pii]
AID - 10.1016/j.cyto.2018.08.030 [doi]
PST - ppublish
SO  - Cytokine. 2018 Nov;111:209-215. doi: 10.1016/j.cyto.2018.08.030. Epub 2018 Aug 
      31.