Antioxidants inhibit cytokine production and suppress NF-kappaB activation in CAPAN-1 and CAPAN-2 cell lines.
Interleukin (IL) -6 and IL-8 are cytokines that have been shown to play a role in several pancreatic diseases, including acute pancreatitis, chronic pancreatitis, and pancreatic adenocarcinoma. Previously, we have demonstrated that tumor necrosis factor-alpha (TNF-alpha) and gram-negative bacterial lipopolysaccharide stimulate production of IL-6 and IL-8 and activation of the transcription factor NF-kappaB in the well-differentiated pancreatic ductal adenocarcinoma cell lines CAPAN-1 and CAPAN-2. In these studies we have examined the effect of chain-breaking and glutathione-enhancing antioxidants on NF-kappaB activation and production of IL-6 and IL-8 in these cell lines. Generally, suppression of NF-kappaB activation correlated well with inhibition of IL-6 and IL-8 secretion. In the CAPAN-2 cell line, antioxidants inhibited both NF-kappaB activation and IL-6 and IL-8 secretion. In the CAPAN-1 cell line, antioxidants generally failed to suppress both NF-kappaB activation and IL-6 and IL-8 secretion. The single exception was the chain-breaking antioxidant butylated hydroxyanisole (BHA), which markedly inhibited IL-6 and IL-8 secretion, but had no effect on NF-kappaB activation. These findings may have implications for the treatment of acute and chronic pancreatitis and pancreatic cancer.
Blanchard
J A
JA
Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, Lexington, USA.
Barve
S
S
Joshi-Barve
S
S
Talwalker
R
R
Gates
L K
LK
D000230:Adenocarcinoma / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D002083:Butylated Hydroxyanisole