HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maldve, R. E. Articles by Fischer, S. M. Search for Related Content PubMed PubMed Citation Articles by Maldve, R. E. Articles by Fischer, S. M. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 41, 873-881, June 2000
Copyright © 2000 by Lipid Research, Inc.

Original Article

Prostaglandin E₂ regulation of cyclooxygenase expression in keratinocytes is mediated via cyclic nucleotide-linked prostaglandin receptors

Correspondence to: Susan M. Fischer

Inflammatory responses are thought to be mediated in part by the prostaglandins derived from arachidonic acid (AA) by the action of prostaglandin H synthase, also referred to as cyclooxygenase (COX). The mitogen-inducible isoform, COX-2, is over-expressed in numerous chronic inflammatory disease conditions and in neoplasms from both human and experimental animal models. COX-1 expression, on the other hand, has been referred to as constitutive or non-inducible. In this study, we present evidence demonstrating autoregulation of prostaglandin (PG) production by the PGs themselves and their precursor, AA. We observed that AA and PGs induced COX-2, as well as COX-1, expression in cultured murine keratinocytes approximately 3 h after treatment. In primary keratinocytes transiently transfected with a full-length COX-2 promoter linked to a luciferase reporter gene, we observed enhanced transcription by AA, PGE₂, and the other prostaglandins. Forskolin, a known activator of adenylate cyclase, and dibutryl-cAMP, a cAMP analog, induced COX-1 and COX-2 mRNA, suggesting that cAMP is a second messenger for COX expression. SQ 22536, an adenylate cyclase inhibitor, inhibited COX-2 mRNA induction by PGE₂ in a dose-dependent manner suggesting that PGE₂-induced expression may be through one of the cAMP-linked PGE₂ receptors.

The results of this study demonstrate that both COX-1 and COX-2 are inducible. Further, both COX isoforms can be up-regulated by their products, the PGs, and this autoregulation probably occurs via prostaglandin receptors linked to a cAMP signal transduction pathway.—Maldve, R. E., Y. Kim, S. J. Muga, and S. M. Fischer. Prostaglandin E₂ regulation of cyclooxygenase expression in keratinocytes is mediated via cyclic nucleotide-linked prostaglandin receptors. J. Lipid Res. 2000. 41: 873;–881.

Supplementary key words: prostaglandins, cyclooxygenase, signal transduction

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				K. M. Ansari, J. E. Rundhaug, and S. M. Fischer Multiple Signaling Pathways Are Responsible for Prostaglandin E2-Induced Murine Keratinocyte Proliferation Mol. Cancer Res., June 1, 2008; 6(6): 1003 - 1016. [Abstract] [Full Text] [PDF]

				K. M. Ansari, Y. M. Sung, G. He, and S. M. Fischer Prostaglandin receptor EP2 is responsible for cyclooxygenase-2 induction by prostaglandin E2 in mouse skin Carcinogenesis, October 1, 2007; 28(10): 2063 - 2068. [Abstract] [Full Text] [PDF]

				H. N. Jabbour, R. W. Kelly, H. M. Fraser, and H. O. D. Critchley Endocrine Regulation of Menstruation Endocr. Rev., February 1, 2006; 27(1): 17 - 46. [Abstract] [Full Text] [PDF]

				Y. M. Sung, G. He, and S. M. Fischer Lack of Expression of the EP2 but not EP3 Receptor for Prostaglandin E2 Results in Suppression of Skin Tumor Development Cancer Res., October 15, 2005; 65(20): 9304 - 9311. [Abstract] [Full Text] [PDF]

				H. Jiang, A. S. Weyrich, G. A. Zimmerman, and T. M. McIntyre Endothelial Cell Confluence Regulates Cyclooxygenase-2 and Prostaglandin E2 Production That Modulate Motility J. Biol. Chem., December 31, 2004; 279(53): 55905 - 55913. [Abstract] [Full Text] [PDF]

				P. Yang, D. Chan, E. Felix, C. Cartwright, D. G. Menter, T. Madden, R. D. Klein, S. M. Fischer, and R. A. Newman Formation and antiproliferative effect of prostaglandin E3 from eicosapentaenoic acid in human lung cancer cells J. Lipid Res., June 1, 2004; 45(6): 1030 - 1039. [Abstract] [Full Text] [PDF]

				R. K. Petersen, C. Jorgensen, A. C. Rustan, L. Froyland, K. Muller-Decker, G. Furstenberger, R. K. Berge, K. Kristiansen, and L. Madsen Arachidonic acid-dependent inhibition of adipocyte differentiation requires PKA activity and is associated with sustained expression of cyclooxygenases J. Lipid Res., December 1, 2003; 44(12): 2320 - 2330. [Abstract] [Full Text] [PDF]

				D. L. Gessell-Lee, V. L. Popov, I. Boldogh, J. P. Olano, and J. W. Peterson Role of Cyclooxygenase Enzymes in a Murine Model of Experimental Cholera Infect. Immun., November 1, 2003; 71(11): 6234 - 6242. [Abstract] [Full Text] [PDF]

				L. Pang, M. Nie, L. Corbett, and A. J. Knox Cyclooxygenase-2 Expression by Nonsteroidal Anti-inflammatory Drugs in Human Airway Smooth Muscle Cells: Role of Peroxisome Proliferator-Activated Receptors J. Immunol., January 15, 2003; 170(2): 1043 - 1051. [Abstract] [Full Text] [PDF]

				K. J. Sales, A. A. Katz, R. P. Millar, and H. N. Jabbour Seminal plasma activates cyclooxygenase-2 and prostaglandin E2 receptor expression and signalling in cervical adenocarcinoma cells Mol. Hum. Reprod., December 1, 2002; 8(12): 1065 - 1070. [Abstract] [Full Text] [PDF]

				M.-H. Wu, H.S. Sun, C.-C. Lin, K.-Y. Hsiao, P.-C. Chuang, H.-A. Pan, and S.-J. Tsai Distinct mechanisms regulate cyclooxygenase-1 and -2 in peritoneal macrophages of women with and without endometriosis Mol. Hum. Reprod., December 1, 2002; 8(12): 1103 - 1110. [Abstract] [Full Text] [PDF]

				Y. Sun, X. M. Tang, E. Half, M. T. Kuo, and F. A. Sinicrope Cyclooxygenase-2 Overexpression Reduces Apoptotic Susceptibility by Inhibiting the Cytochrome c-dependent Apoptotic Pathway in Human Colon Cancer Cells Cancer Res., November 1, 2002; 62(21): 6323 - 6328. [Abstract] [Full Text] [PDF]

				B. Hinz and K. Brune Cyclooxygenase-2---10 Years Later J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 367 - 375. [Abstract] [Full Text] [PDF]

				K. J. Sales, A. A. Katz, B. Howard, R. P. Soeters, R. P. Millar, and H. N. Jabbour Cyclooxygenase-1 Is Up-Regulated in Cervical Carcinomas: Autocrine/Paracrine Regulation of Cyclooxygenase-2, Prostaglandin E Receptors, and Angiogenic Factors by Cyclooxygenase-1 Cancer Res., January 1, 2002; 62(2): 424 - 432. [Abstract] [Full Text] [PDF]