The effects of nuclear factor-kappa B in pancreatic stellate cells on inflammation and fibrosis of chronic pancreatitis.

Abstract

The activation of pancreatic stellate cells (PSCs) plays a critical role in the progression of pancreatic fibrosis. Nuclear factor‐kappa B (NF‐κB) is associated with chronic pancreatitis (CP). Previous evidence indicated that NF‐κB in acinar cells played a double‐edged role upon pancreatic injury, whereas NF‐κB in inflammatory cells promoted the progression of CP. However, the effects of NF‐κB in PSCs have not been studied. In the present study, using two CP models and RNAi strategy of p65 in cultured PSCs, we found that the macrophage infiltration and MCP‐1 expression were increased, and the NF‐κBp65 protein level was elevated. NF‐κBp65 was co‐expressed with PSCs. In vitro, TGF‐β1 induced overexpression of the TGF‐β receptor 1, phosphorylated TGF‐β1–activated kinase 1 (p‐TAK1) and NF‐κB in the PSCs. Moreover, the concentration of MCP‐1 in the supernatant of activated PSCs was elevated. The migration of BMDMs was promoted by the supernatant of activated PSCs. Further knockdown of NF‐κBp65 in PSCs resulted in a decline of BMDM migration, accompanied by a lower production of MCP‐1. These findings indicate that TGF‐β1 can induce the activation of NF‐κB pathway in PSCs by regulating p‐TAK1, and the NF‐κB pathway in PSCs may be a target of chronic inflammation and fibrosis.