PMID- 8766541 OWN - NLM STAT- MEDLINE DCOM- 19960916 LR - 20131121 IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 26 IP - 7 DP - 1996 Jul TI - Selective suppression of endothelial cell activation by arachidonic acid. PG - 1417-23 AB - Endothelial cell (EC) activation plays a key role in inflammation, thrombosis and organ rejection. Normally, EC are in a quiescent state in which their function is to prevent coagulation and thrombosis, and to participate in the regulation of leukocyte migration from the bloodstream into the tissue. Upon activation with cytokines or other stimuli, EC up-regulate a number of genes, including E-selectin (ELAM-1), intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, interleukin (IL)-1, IL-8, tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), MCP-1 (monocyte chemoattractant protein-1) and endothelial cell inducible gene (ECI-6). Arachidonic acid (AA) is produced by several cell types, including EC, and acts on various cells. We report here that AA inhibits the up-regulation of some, but not all genes that are induced with EC activation in a dose-dependent manner. AA suppresses TNF-alpha, IL-1 alpha, LPS or PMA-induced E-selectin expression, as well as mRNA accumulation of E-selectin, ICAM-1 and IL-8 stimulated by TNF-alpha. The inhibition appears to be at the level of transcription. At the same time under the same conditions AA does not, repress mRNA accumulation for PAI-1, ECI-6, MCP-1 and VCAM-1. We suggest that the induced expression of AA with EC activation may result in a negative feedback loop regulating further activation. FAU - Stuhlmeier, K M AU - Stuhlmeier KM AD - New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215, USA. kstuhlme@nedhmail.nedh.harvard.edu FAU - Tarn, C AU - Tarn C FAU - Csizmadia, V AU - Csizmadia V FAU - Bach, F H AU - Bach FH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (E-Selectin) RN - 0 (Immunosuppressive Agents) RN - 27YG812J1I (Arachidonic Acid) SB - IM MH - Animals MH - Aorta/cytology MH - Arachidonic Acid/metabolism/*pharmacology MH - E-Selectin/drug effects/genetics MH - Endothelium, Vascular/*drug effects/immunology/metabolism MH - Gene Expression Regulation/drug effects/immunology MH - Immunosuppressive Agents/*pharmacology MH - Swine MH - Transcription, Genetic/drug effects MH - Up-Regulation/drug effects/genetics/immunology EDAT- 1996/07/01 00:00 MHDA- 1996/07/01 00:01 CRDT- 1996/07/01 00:00 PHST- 1996/07/01 00:00 [pubmed] PHST- 1996/07/01 00:01 [medline] PHST- 1996/07/01 00:00 [entrez] AID - 10.1002/eji.1830260703 [doi] PST - ppublish SO - Eur J Immunol. 1996 Jul;26(7):1417-23. doi: 10.1002/eji.1830260703.