Figure 7.

Proposed network for AhR-Src-STAT3-IL-10 signaling pathway in inflammatory macrophages. AhR expression is highly enhanced in LPS-induced inflammatory macrophages via the NF-κB pathway. AhR binds to the IL-10-promoter, but does not affect the transcriptional activity of IL-10. Increased AhR in the cytoplasm upregulates the tyrosine phosphorylation of Src, which can be suppressed by selective Src inhibitors (PP2 and dasatinib). STAT3 is also activated by phosphorylation of tyrosine 705, triggered by Src tyrosine kinase and suppressed by selective STAT3 inhibitors (cryptotanshinone and BP-1-102). STAT3 activation is independent of IL-10 autocrine feedback, Akt/mTOR, and MAPK pathways. The activated signaling pathway promotes LPS-induced IL-10 expression. Overall, AhR-associated Src activity is responsible for the tyrosine phosphorylation of STAT3 and IL-10 expression in LPS-induced inflammatory macrophages.