| TLR4-dependent induction of vascular adhesion molecule-1 in rheumatoid arthritis synovial fibroblasts: Roles of cytosolic phospholipase A(2)alpha/cyclooxygenase-2. | |
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MedLine Citation:
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PMID: 20112284 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4)-mediated signaling pathways have caught the attention of strategies designed for rheumatoid arthritis (RA). In this study, we identified that cPLA(2)alpha acted as a modulator of LPS-induced VCAM-1 expression and THP-1 (human acute monocytic leukemia cell line) adherence. Treatment of RA synovial fibroblasts (RASFs) with LPS, a TLR4 agonist, promoted the VCAM-1 expression and THP-1 adherence which were decreased by pretreatment with a selective cytosolic phospholipase A(2) (cPLA(2)) inhibitor (AACOCF(3)), implying the involvement of cPLA(2)alpha in these responses. This notion was further confirmed by knockdown of cPLA(2)alpha expression by transfection with cPLA(2)alpha small interfering RNA (siRNA) leading to a decrease in VCAM-1 expression and THP-1 adherence induced by LPS. Subsequently, the LPS-stimulated cPLA(2)alpha phosphorylation was attenuated by pretreatment with a MEK1/2 inhibitor (U0126), suggesting that LPS-stimulated cPLA(2)alpha phosphorylation and activity are mediated through an ERK-dependent mechanism. Moreover, COX-2-derived PGE(2) production appeared to involve in LPS-induced VCAM-1 expression which was attenuated by pretreatment with selective COX-2 inhibitors (NS-398 and celecoxib), transfection with COX-2 siRNA, or PGE(2) receptor antagonists. In addition, pretreatment with ecosapentaenoic acid (EPA), a substrate competitor of arachidonic acid (AA), also blocked LPS-induced VCAM-1 mRNA and protein expression, and THP-1 adherence. Collectively, these results suggest that LPS-induced VCAM-1 expression and adhesion of THP-1 cells are mediated through the TLR4/ERK/cPLA(2)alpha phosphorylation and COX-2 expression/PGE(2) synthesis in RASFs. |
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Authors:
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Cheng-Ying Wu; Pei-Ling Chi; Hsi-Lung Hsieh; Shue-Fen Luo; Chuen-Mao Yang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 223 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-03-01 Completed Date: 2010-05-06 Revised Date: 2012-05-25 |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 480-91 Citation Subset: IM |
Affiliation:
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Department of Physiology and Pharmacology, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amine Oxidase (Copper-Containing)
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genetics,
metabolism* Arachidonic Acids / pharmacology Arthritis, Rheumatoid / metabolism, physiopathology Cell Adhesion / physiology Cell Adhesion Molecules / genetics, metabolism* Cell Line Cells, Cultured Cyclooxygenase 2 / drug effects, genetics, metabolism* Cyclooxygenase 2 Inhibitors / pharmacology Dinoprostone / biosynthesis Eicosapentaenoic Acid / pharmacology Enzyme Inhibitors / pharmacology Extracellular Signal-Regulated MAP Kinases / metabolism Fibroblasts / cytology, metabolism* Group IV Phospholipases A2 / antagonists & inhibitors, genetics, metabolism* Humans Inflammation Mediators / pharmacology Lipopolysaccharides / pharmacology RNA Interference RNA, Messenger / drug effects Receptors, Prostaglandin E / antagonists & inhibitors, metabolism Signal Transduction / physiology Synovial Membrane / cytology, metabolism*, physiopathology Toll-Like Receptor 4 / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 0/Cell Adhesion Molecules; 0/Cyclooxygenase 2 Inhibitors; 0/Enzyme Inhibitors; 0/Inflammation Mediators; 0/Lipopolysaccharides; 0/RNA, Messenger; 0/Receptors, Prostaglandin E; 0/TLR4 protein, human; 0/Toll-Like Receptor 4; 149301-79-1/arachidonyltrifluoromethane; 1553-41-9/Eicosapentaenoic Acid; 363-24-6/Dinoprostone; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 1.4.3.21/AOC3 protein, human; EC 1.4.3.6/Amine Oxidase (Copper-Containing); EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.1.1.4/Group IV Phospholipases A2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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