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Pancreatic stellate cells (PSCs) are activated by inflammatory stimuli, such as TNF-α or viral infection. Activated PSCs play a cru cial role in the development of chronic pancreatitis. Polyinosinic-polycytidylic acid (poly (I:C)) is structurally similar to double-strand ed RNA and mimics viral infection. Docosahexaenoic acid (DHA) exhibits anti-inflammatory activity. It inhibited fibrotic mediators and reduced NF-κB activity in the pancreas of mice with chronic pancreatitis. The present study aimed to investigate whether DHA could suppress cytokine expression in PSCs isolated from rats. Cells were pre-treated with DHA or the antioxidant N-acetylcysteine (NAC) and stimulated with TNF-α or poly (I:C). Treatment with TNF-α or poly (I:C) increased the expression of monocyte chemo attractant protein 1 (MCP-1) and chemokine C-X3-C motif ligand 1 (CX3CL1), which are known chemoattractants, and enhanced intracellular and mitochondrial reactive oxygen species (ROS) production and NF-κB activity, but reduced mitochondrial membrane potential (MMP). Increased intracellular and mitochondrial ROS accumulation, cytokine expression, MMP disruption, and NF-κB activation were all prevented by DHA in TNF-α- or poly (I:C)-treated PSCs. NAC suppressed TNF-α- or poly (I:C)-induced expres sion of MCP-1 and CX3CL1. In conclusion, DHA inhibits poly (I:C)- or TNF-α-induced cytokine expression and NF-κB activation by reducing intracellular and mitochondrial ROS in PSCs. Consumption of DHA-rich foods may be beneficial in preventing chronic pancreatitis by inhibiting cytokine expression in PSCs.
Key Words Cytokines, Docosahexaenoic acid, Pancreatic stellate cells, Reactive oxygen species
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참고문헌 (71)
참고문헌 신청
Singh VK / 2019 / Diagnosis and management of chronic pancreatitis : a review / JAMA 322:2422~2434
Majumder S / 2016 / Chronic pancreatitis / Lancet 387:1957~1966
Masamune A / 2009 / Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis / Clin Gastroenterol Hepatol 7(11 Suppl):S48~S54
Marra F / 2005 / Renaming cytokines : MCP-1, major chemokine in pancreatitis / Gut 54:1679~1681
Uchida M / 2013 / ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1 release in pancreatic stellate cells / Lab Invest 93:41~53
Majumder S / 2016 / Chronic pancreatitis / Lancet 387:1957~1966
Masamune A / 2009 / Roles of pancreatic stellate cells in pancreatic inflammation and fibrosis / Clin Gastroenterol Hepatol 7(11 Suppl):S48~S54
Marra F / 2005 / Renaming cytokines : MCP-1, major chemokine in pancreatitis / Gut 54:1679~1681
Uchida M / 2013 / ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1 release in pancreatic stellate cells / Lab Invest 93:41~53
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