Mesenchymal stem cells regulate M1 polarization of peritoneal macrophages through the CARD9-NF-κB signaling pathway in severe acute pancreatitis

Macrophages release large numbers of proinflammatory cytokines that trigger inflammatory cascade reactions, which promote the rapid development of severe acute pancreatitis (SAP) from local to systemic inflammation. The ability of mesenchymal stem cells (MSCs) to suppress inflammation is related to inhibition of M1 polarization of macrophages. Our previous studies revealed that caspase recruitment domain protein 9 (CARD9) was involved in SAP inflammation and activation of the CARD9-NF-κB signaling pathway plays an important proinflammatory role in SAP. At present, there is no effective treatment to control the inflammatory response in SAP. Therefore, the aim of the present study was to determine whether MSCs regulate the polarization of macrophages through the CARD9-NF-κB signaling pathway in SAP.

Short hairpin RNA interference technology and coculture in vitro were used to assess the activation status of the CARD9-NF-κB signal pathway in macrophages. Furthermore, flow cytometry was used to determine the polarization state of macrophages.

The results showed MSCs inhibited CARD9 expression in vivo and in vitro (P < .05), alleviated inflammation induced by proinflammatory cytokines, and inhibited the phosphorylation of NF-κB in macrophages both in vivo and in vitro. Meanwhile, MSCs downregulated the CARD9-NF-κB signal pathway and inhibited M1 polarization of macrophages.

In conclusion, MSCs regulate M1 polarization of peritoneal macrophages through the CARD9-NF-κB signaling pathway in SAP and transplantation of MSCs presents an effective treatment option for SAP.