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Interleukin-1beta induces cyclo-oxygenase-2 expression in gastric cancer cells by the p38 and p44/42 mitogen-activated protein kinase signaling pathways.
J Gastroenterol Hepatol. 2001 Oct; 16(10):1098-104.JG

Abstract

BACKGROUND AND AIMS

Cyclo-oxygenase-2 (COX-2) is the inducible enzyme in the gastric mucosa responsible for prostaglandin production during inflammation and ulcer healing. The regulation of COX-2 gene expression in gastric epithelial cells is not well understood. In this study, we investigated the effect of interleukin (IL)-1beta on COX-2 expression in the human gastric cancer cell, and explored the signaling pathways involved.

METHODS

Gastric cancer cell line AGS was treated with IL-1beta or the inhibitors of mitogen-activated protein-Erk kinase (MEK) and p38 mitogen-activated protein (MAP) kinase prior to the addition of IL-1beta. The COX-2 mRNA or protein levels were measured by using RT-PCR or western blot analysis, respectively. Prostaglandin E2 (PGE2) production/secretion was determined by using the prostaglandin E2 EIA assay. The phosphorylation/activation of p44/42 and p38 MAP kinases were determined by using western blot analysis and using phospho-specific antibodies.

RESULTS

Interleukin-1beta treatment dose- and time-dependently increased COX-2 mRNA and protein expression levels, and enhanced PGE2 production/secretion in AGS cells. In contrast, IL-1beta had no effect on the level of the constitutively expressed COX-1. In parallel to the increase of COX-2, we showed that p44/42 and p38 MAP kinase activities were also upregulated by IL-1beta treatment. To demonstrate the cause-effect relationship, we showed that inhibition of MEK and p38 MAP kinase with specific inhibitors suppressed IL-1beta-mediated increases in COX-2 mRNA and protein levels, and the PGE2 production.

CONCLUSIONS

Our results demonstrated that in human gastric cancer cells, IL-1beta upregulates the COX-2 gene expression through the activation of MEK/p44/42 and p38 MAP kinases pathway.

Authors+Show Affiliations

Department of Medicine, University of Hong Kong, Hong Kong.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11686835

Citation

Fan, X M., et al. "Interleukin-1beta Induces Cyclo-oxygenase-2 Expression in Gastric Cancer Cells By the P38 and P44/42 Mitogen-activated Protein Kinase Signaling Pathways." Journal of Gastroenterology and Hepatology, vol. 16, no. 10, 2001, pp. 1098-104.
Fan XM, Wong BC, Lin MC, et al. Interleukin-1beta induces cyclo-oxygenase-2 expression in gastric cancer cells by the p38 and p44/42 mitogen-activated protein kinase signaling pathways. J Gastroenterol Hepatol. 2001;16(10):1098-104.
Fan, X. M., Wong, B. C., Lin, M. C., Cho, C. H., Wang, W. P., Kung, H. F., & Lam, S. K. (2001). Interleukin-1beta induces cyclo-oxygenase-2 expression in gastric cancer cells by the p38 and p44/42 mitogen-activated protein kinase signaling pathways. Journal of Gastroenterology and Hepatology, 16(10), 1098-104.
Fan XM, et al. Interleukin-1beta Induces Cyclo-oxygenase-2 Expression in Gastric Cancer Cells By the P38 and P44/42 Mitogen-activated Protein Kinase Signaling Pathways. J Gastroenterol Hepatol. 2001;16(10):1098-104. PubMed PMID: 11686835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interleukin-1beta induces cyclo-oxygenase-2 expression in gastric cancer cells by the p38 and p44/42 mitogen-activated protein kinase signaling pathways. AU - Fan,X M, AU - Wong,B C, AU - Lin,M C, AU - Cho,C H, AU - Wang,W P, AU - Kung,H F, AU - Lam,S K, PY - 2001/11/1/pubmed PY - 2002/2/8/medline PY - 2001/11/1/entrez SP - 1098 EP - 104 JF - Journal of gastroenterology and hepatology JO - J. Gastroenterol. Hepatol. VL - 16 IS - 10 N2 - BACKGROUND AND AIMS: Cyclo-oxygenase-2 (COX-2) is the inducible enzyme in the gastric mucosa responsible for prostaglandin production during inflammation and ulcer healing. The regulation of COX-2 gene expression in gastric epithelial cells is not well understood. In this study, we investigated the effect of interleukin (IL)-1beta on COX-2 expression in the human gastric cancer cell, and explored the signaling pathways involved. METHODS: Gastric cancer cell line AGS was treated with IL-1beta or the inhibitors of mitogen-activated protein-Erk kinase (MEK) and p38 mitogen-activated protein (MAP) kinase prior to the addition of IL-1beta. The COX-2 mRNA or protein levels were measured by using RT-PCR or western blot analysis, respectively. Prostaglandin E2 (PGE2) production/secretion was determined by using the prostaglandin E2 EIA assay. The phosphorylation/activation of p44/42 and p38 MAP kinases were determined by using western blot analysis and using phospho-specific antibodies. RESULTS: Interleukin-1beta treatment dose- and time-dependently increased COX-2 mRNA and protein expression levels, and enhanced PGE2 production/secretion in AGS cells. In contrast, IL-1beta had no effect on the level of the constitutively expressed COX-1. In parallel to the increase of COX-2, we showed that p44/42 and p38 MAP kinase activities were also upregulated by IL-1beta treatment. To demonstrate the cause-effect relationship, we showed that inhibition of MEK and p38 MAP kinase with specific inhibitors suppressed IL-1beta-mediated increases in COX-2 mRNA and protein levels, and the PGE2 production. CONCLUSIONS: Our results demonstrated that in human gastric cancer cells, IL-1beta upregulates the COX-2 gene expression through the activation of MEK/p44/42 and p38 MAP kinases pathway. SN - 0815-9319 UR - https://www.unboundmedicine.com/medline/citation/11686835/Interleukin_1beta_induces_cyclo_oxygenase_2_expression_in_gastric_cancer_cells_by_the_p38_and_p44/42_mitogen_activated_protein_kinase_signaling_pathways_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0815-9319&date=2001&volume=16&issue=10&spage=1098 DB - PRIME DP - Unbound Medicine ER -