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IL‐6 expression and secretion in HET‐1 cells is associated with Cox‐2
Author(s) -
Rogaczewski Aaron L,
Nelson Victoria M,
Ali Irshad,
Binion David G,
Rafiee Parvaneh,
Shaker Reza
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1079-d
Subject(s) - wortmannin , secretion , mapk/erk pathway , pi3k/akt/mtor pathway , cytokine , chemistry , protein kinase b , p38 mitogen activated protein kinases , microbiology and biotechnology , signal transduction , biology , immunology , biochemistry
IL‐6 is a pleiotropic cytokine, being both a mitogen and inhibitor of apoptosis. Involvement of IL‐6 in various diseases including carcinogenesis has been established. The aim of this study was to determine role of IL‐6 expression and secretion on Cox‐2 in activated HET‐1 cells. HET‐1 cell cultures were activated with growth media containing IL‐6 (100U/ml) or acidified growth media (pH 4.5). Pharmacologic inhibitors including NS398 (Cox‐2), Wortmannin (PI3k/Akt), SB203580 (p38 MAPK) and PD098059 (MEK/ERK) were used to identify the signaling pathways involving IL‐6 and Cox‐2. Following activation, the cells were rinsed to remove any residual activators and inhibitors, and standard growth media was replaced. IL‐6 and PGE2 production in culture media was determined by ELISA. mRNA and protein expression were determined by RT‐PCR and Western blotting. Both acidic pH and exogenous IL‐6 enhanced IL‐6 production. Wortmannin did not affect IL‐6 secretion, whereas NS398 further enhanced IL‐6 production in both activated conditions. Acidic pH also enhanced PGE2 production, which was inhibited by NS398. Conversely, exogenous IL‐6 exerted an unexpected inhibition of PGE2, and NS398 led to a further unexpected reversal of the inhibition. Wortmannin did not affect PGE2 secretion in either activated condition. These data demonstrate a possible novel pathway mechanism between IL‐6 and Cox‐2 not previously observed. Supported by Digestive Disease Center and Cancer Center (P.R., D.G.B.)