Docosahexaenoic Acid Inhibits Cytokine Expression through Suppression of NF‐κB Activation in Rat Pancreatic Stellate Cells

Abstract

Pancreatic stellate cells (PSCs), when activated by cytokine such as tumor necrosis factor α (TNF‐α), plays an important role in the development of chronic pancreatitis. Induction of inflammatory cytokines and fibrotic proteins contribute to development of chronic pancreatitis. NF‐κB is known to induce pancreatic and systemic inflammatory response. Docosahexaenoic acid (DHA), omega 3‐polyunsaturated fatty acid, shows anti‐inflammatory and anti‐fibrotic effects.In the present study, we investigated whether DHA decreases expression of inflammatory cytokines (MCP‐1, CX3CL1) and fibrotic proteins (alpha smooth muscle actin, α‐SMA; desmin, collagen such as COL1A1 and COL1A1; transforming growth factor beta 1,TGF‐β1) as well as and NF‐κB activity in PSCs exposed to PSCs activating factor TNF‐α.The cells were isolated from pancreas of the rat and cultured in the presence or absence of DHA. mRNA and protein levels were determined by real time PCR and ELISA or western blot analysis.The results show that expression of inflammatory cytokines (MCP‐1, CX3CL1) and fibrotic proteins (α‐SMA, desmin, COL1A1, COL1A1, TGF‐β1), and DNA binding activity of NF‐κB were increased by TNF‐α in PSCs. DHA suppressed TNF‐α‐induced expressions of cytokines and fibrotic proteins by inhibiting NF‐κB activity in PSCs.In conclusion, DHA may inhibit inflammation and fibrosis in pancreatic stellate cells exposed to inflammatory stimulus such as TNF‐α. DHA may be beneficial for preventing development of chronic pancreatitis.Support or Funding InformationThis study was supported by a grant (NRF‐2015R1A2A2A01004855) from the NRF of Korea.