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.
Highlights
Inflammation is a double-edged sword of the innate immune response
We investigated the expression of aryl hydrocarbon receptor (AhR) in LPS-stimulated mouse macrophages, which were identified according to the dual presence of F4/80 and CD11b (Figure S1)
The results revealed that LPS-induced AhR expression was mediated by the NF-κB pathway in macrophages
Summary
Inflammation is a double-edged sword of the innate immune response. To limit the undesirable consequences of excessive inflammation, factors that modulate the initiation phase and the resolution phase of inflammation can determine the nature of the inflammatory response [1]. Recent studies have identified the molecular functions of AhR in the immune system during steady state and during infection and inflammation [3,4,5,6]. AhR-KO mice were hypersensitive to LPS-induced septic shock, mainly as a result of macrophage dysfunction. Consistent with their enhanced susceptibility to LPS treatment, AhR-KO mice showed markedly increased plasma levels of IL-1β, IL-18, IL-6, and
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
