PACAP Improves Macrophage M1 Polarization and Inflammatory Response by Regulating NF-κB and MAPKs Pathways

Abstract

Inflammation is an important defense mechanism evolved by the host to defend against external threats. But an excessive inflammatory response can lead to a variety of inflammatory diseases. Macrophage M1 polarization is a key factor in inducing inflammatory response, and inhibiting macrophage M1 polarization is of great significance for regulating inflammatory diseases. PACAP is an anti-inflammatory neuropeptide, but its mechanism of action on macrophage polarization and inflammatory responses is unclear. The macrophage M1 polarization and inflammation model was constructed using lipopolysaccharide (LPS), and then treated with PACAP. The results showed that PACAP significantly inhibited the LPS-induced expression of M1 polarization marker genes and inflammatory factors in macrophages, and down-regulated the phosphorylation of IKK2/IκBα/NF-κB, while PACAP also inhibited the phosphorylation of JNK/p38. Thus， PACAP improved LPS-induced macrophage M1 polarization and inflammatory response by regulating NF-κB and MAPKs signaling pathways.