The role of the α7 nicotinic acetylcholine receptor in promoting M2 macrophage polarization at inflammatory sites.

Abstract

The α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages exerts anti-inflammatory effects by suppressing the JAK/STAT and NF-κB pathways. Although the role of α7nAChR in immunoregulatory mechanisms in "individual" macrophages is established, studies on α7nAChR in an "overall population" of macrophages, including M1/M2 polarity, remain limited. Therefore, we examined the role of α7nAChR in M1/M2 polarity in inflammation. We generated peritonitis mouse models via LPS treatment and sterile intestinal manipulation in wild-type and α7nAChR-deficient mice. M1/M2 macrophage polarization was measured using PCR and flow cytometry. THP-1 and human peripheral blood mononuclear cells (hPBMC)-derived monocytes were treated with the α7nAChR agonist PNU-282987 during differentiation into M1/M2 macrophages. α7nAChR deficiency upregulated mRNA expression of the M1 marker and downregulated the M2 marker in a peritoneal cell population. Flow cytometry analysis revealed that the proportion of M2 macrophages in the peritoneal cell population decreased in α7nAChR-deficient mice in both models. In splenectomized LPS-treated wild-type mice, the proportion of M2 macrophages in the peritoneal cell population was reduced compared to that in sham-operated LPS-treated mice. The M2 marker CD206 and IL10 were upregulated in PNU-282987-treated THP-1 and hPBMC-derived macrophages. These results revealed that α7nAChR exerted M2-enhancing effects with the mechanism suggestively acting in the spleen.