1. Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway.
- Author
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Zhu J, Luo L, Tian L, Yin S, Ma X, Cheng S, Tang W, Yu J, Ma W, Zhou X, Fan X, Yang X, Yan J, Xu X, Lv C, and Liang H
- Subjects
- Adoptive Transfer, Animals, HEK293 Cells, Humans, Inflammation genetics, Inflammation metabolism, Interleukin-10 genetics, Interleukin-10 metabolism, Lipopolysaccharides pharmacology, Macrophages drug effects, Macrophages metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Peritonitis immunology, Peritonitis metabolism, Peritonitis therapy, RAW 264.7 Cells, Receptors, Aryl Hydrocarbon genetics, Receptors, Aryl Hydrocarbon metabolism, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, src-Family Kinases genetics, src-Family Kinases metabolism, Inflammation immunology, Interleukin-10 immunology, Macrophages immunology, Receptors, Aryl Hydrocarbon immunology, STAT3 Transcription Factor immunology, src-Family Kinases immunology
- Abstract
The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-κB pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR-overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10 expression by inflammatory macrophages. Adoptive transfer of AhR-expressing macrophages protected mice against LPS-induced peritonitis associated with high IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling pathway as a critical pathway in the immune regulation of inflammatory macrophages, It suggests that AhR may be a potential therapeutic target in immune response.
- Published
- 2018
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