Abstract
Excessive leukocyte proliferation and proinflammatory mediators release represent common phenomena in several chronic inflammatory diseases. Multiple evidences identify lysophosphatidic acid (LPA), a small lipid endowed with pleiotropic activities, as an important modulator of both proliferation and activation of different cell types involved in several inflammation-associated pathologies. However, its possible role on monocyte proinflammatory activation is not fully understood yet. Aim of the present study was to investigate LPA effects on THP-1 cells in terms of proliferation, reactive oxygen intermediates (ROI) production and release of arachidonic acid-derived inflammatory mediators. Actually, LPA significantly increased both DNA synthesis and ROI production as well as prostaglandin E(2) release and the upregulation of LPA(3) receptor expression. These findings identified LPA as both a growth factor and a triggering mediator of proinflammatory response in THP-1 cells.
MeSH terms
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Arachidonic Acid / metabolism*
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Cell Line
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Cell Proliferation* / drug effects
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DNA Replication
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Dinoprostone / metabolism
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Enzyme Activation
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Humans
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Inflammation / metabolism
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Inflammation Mediators / metabolism*
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Isoxazoles / pharmacology
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Leukotriene B4 / metabolism
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Lysophospholipids / metabolism*
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Monocytes / drug effects
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Monocytes / metabolism*
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NADPH Oxidases / metabolism
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Propionates / pharmacology
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RNA, Messenger / metabolism
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Reactive Oxygen Species / metabolism*
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Receptors, Lysophosphatidic Acid / antagonists & inhibitors
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Receptors, Lysophosphatidic Acid / genetics
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Receptors, Lysophosphatidic Acid / metabolism
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Time Factors
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Up-Regulation
Substances
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3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid
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Inflammation Mediators
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Isoxazoles
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Lysophospholipids
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Propionates
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RNA, Messenger
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Reactive Oxygen Species
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Receptors, Lysophosphatidic Acid
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Leukotriene B4
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Arachidonic Acid
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NADPH Oxidases
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Dinoprostone
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lysophosphatidic acid