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

Zhihong Zhang; Zuguo Liu; Kathryn E Meier

doi:10.1152/ajpcell.00523.2005

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

Journal article

Peer reviewed

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

Zhihong Zhang, Zuguo Liu and Kathryn E Meier

American Journal of Physiology: Cell Physiology, Vol.291(5), pp.C1089-1098

11/2006

DOI: https://doi.org/10.1152/ajpcell.00523.2005

Handle:

https://hdl.handle.net/2376/117502

PMID: 16760261

Abstract

Propionates - pharmacology

Lysophospholipids - metabolism

Epithelial Cells - drug effects

Humans

Receptors, Lysophosphatidic Acid - genetics

Extracellular Signal-Regulated MAP Kinases - metabolism

RNA, Messenger - metabolism

Inflammation Mediators - agonists

Cornea - drug effects

Inflammation Mediators - metabolism

Lysophospholipids - pharmacology

Cornea - cytology

p38 Mitogen-Activated Protein Kinases - metabolism

Epithelial Cells - cytology

Proto-Oncogene Proteins c-akt - metabolism

Cell Line

RNA, Messenger - genetics

Cells, Cultured

Enzyme Activation - drug effects

Interleukin-1 - pharmacology

Gene Expression Regulation - drug effects

Isoxazoles - pharmacology

Tumor Necrosis Factor-alpha - pharmacology

Signal Transduction - drug effects

Lipopolysaccharides - pharmacology

Cell Proliferation - drug effects

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-1beta, and TNF-alpha. LPS, IL-1beta, and TNF-alpha, 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 LPA(1)/EDG-2, LPA(2)/EDG-4, and LPA(3)/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.

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Title: Lysophosphatidic acid as a mediator for proinflammatory agonists in a human corneal epithelial cell line
Creators: Zhihong Zhang - Dept. of Pharmaceutical Sciences, Washington State University, Pullman, WA 99164-6534, USA
Zuguo Liu
Kathryn E Meier
Publication Details: American Journal of Physiology: Cell Physiology, Vol.291(5), pp.C1089-1098
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: United States
Identifiers: 99900548142301842
Language: English
Resource Type: Journal article

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

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