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) All Versions of this Article: 291/5/C1089    most recent 00523.2005v1 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 ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Zhang, Z. Articles by Meier, K. E. Search for Related Content PubMed PubMed Citation Articles by Zhang, Z. Articles by Meier, K. E.

RECEPTORS AND SIGNAL TRANSDUCTION

Lysophosphatidic acid as a mediator for proinflammatory agonists in a human corneal epithelial cell line

¹Department of Pharmaceutical Sciences, Washington State University, Pullman, Washington; and ²Zhongshan Ophthalmic Center, Sun Yat-sen University, Key Laboratory of Ophthalmology, Ministry of Education, Guangzhou, People's Republic of China

Submitted 18 October 2005 ; accepted in final form 26 May 2006

Lysophosphatidic acid (LPA) refers to a family of small phospholipid mediators that are generated in response to agonist stimulation in diverse cell types. LPA binds to G protein-coupled receptors to elicit numerous biological responses, including proliferation and inflammation. In this study, LPA production and response were characterized in a human corneal epithelial cell line, 2.040 pRSV-T. LPA levels in cells and medium are increased by exogenous 18:1 LPA (oleoyl-LPA), LPS, IL-1, and TNF-. LPS, IL-1, and TNF-, which mediate ocular inflammation, stimulate activation of p38, ERK, and Akt kinases in the corneal cell line. Similar responses are elicited by 18:1 LPA. Pertussis toxin (PTX) blocks LPA-induced activation of p38 and ERK but only slightly inhibits LPA-induced activation of Akt. All of the agonists tested, including LPA, stimulate proliferation of 2.040 pRSV-T cells. In these cells, both Akt and ERK pathways are important for LPA-induced proliferation. Thus PTX only partially suppresses the mitogenic response to LPA. Transcripts for the LPA receptors LPA₁/EDG-2, LPA₂/EDG-4, and LPA₃/EDG-7 are expressed by the corneal cell line. Ki16425, an antagonist for LPA receptors, was used to explore the autocrine role of LPA. LPA-induced activations of p38, ERK, and Akt kinases, as well as proliferation, are inhibited by Ki16425. Ki16425 partially inhibits signal transduction and proliferation induced by the inflammatory agents tested. We conclude that LPA, produced in corneal epithelial cells in response to inflammatory agonists, contributes to mediating the mitogenic responses to these agonists in an autocrine fashion.

phospholipid mediators; protein phosphorylation; G protein-coupled receptors; inflammation

This article has been cited by other articles:

				K. M. Kassel, P. R. Dodmane, N. A. Schulte, and M. L. Toews Lysophosphatidic Acid Induces Rapid and Sustained Decreases in Epidermal Growth Factor Receptor Binding via Different Signaling Pathways in BEAS-2B Airway Epithelial Cells J. Pharmacol. Exp. Ther., June 1, 2008; 325(3): 809 - 817. [Abstract] [Full Text] [PDF]

				K.-P. Xu, J. Yin, and F.-S. X. Yu Lysophosphatidic Acid Promoting Corneal Epithelial Wound Healing by Transactivation of Epidermal Growth Factor Receptor Invest. Ophthalmol. Vis. Sci., February 1, 2007; 48(2): 636 - 643. [Abstract] [Full Text] [PDF]