Histamine directly and synergistically with lipopolysaccharide stimulates cyclooxygenase-2 expression and prostaglandin I(2) and E(2) production in human coronary artery endothelial cells.
Although histamine plays an essential role in inflammation, its influence on cyclooxygenases (COX) and prostanoid homeostasis is not well understood. In this study, we investigated the effects of histamine on the expression of COX-1 and COX-2 and determined their contribution to the production of PGE(2), prostacyclin (PGI(2)), and thromboxane A(2) in human coronary artery endothelial cells (HCAEC). Incubation of HCAEC monolayers with histamine resulted in marked increases in the expression of COX-2 and production of PGI(2) and PGE(2) with no significant change in the expression of COX-1. Histamine-induced increases in PGI(2) and PGE(2) production were due to increased expression and function of COX-2 because gene silencing by small interfering RNA or inhibition of the catalytic activity by a COX-2 inhibitor blocked prostanoid production. The effects of histamine on COX-2 expression and prostanoid production were mediated through H(1) receptors. In addition to the direct effect, histamine was found to amplify LPS-stimulated COX-2 expression and PGE(2) and PGI(2) production. In contrast, histamine did not stimulate thromboxane A(2) production in resting or LPS-activated HCAEC. Histamine-induced increases in the production of PGE(2) and PGI(2) were associated with increased expression of mRNA encoding PGE(2) and PGI(2) synthases. The physiological role of histamine on the regulation of COX-2 expression in the vasculature is indicated by the findings that the expression of COX-2 mRNA, but not COX-1 mRNA, was markedly reduced in the aortic tissues of histidine decarboxylase null mice. Thus, histamine plays an important role in the regulation of COX-2 expression and prostanoid homeostasis in vascular endothelium.
Tan
Xiaoyu
X
Division of Allergy, Clinical Immunology, and Rheumatology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Essengue
Suzanne
S
Talreja
Jaya
J
Reese
Jeff
J
Stechschulte
Daniel J
DJ
Dileepan
Kottarappat N
KN
D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics*; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D020868:Gene Silencing / Q000187:drug effects; D006632:Histamine / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000172:deficiency / Q000276:immunology; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013329:Structure-Activity Relationship; D013928:Thromboxane A2 / Q000096:biosynthesis
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011969:Receptors, Histamine H1; D013928:Thromboxane A2; D006632:Histamine; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D000587:Oxidoreductases Acting on CH-NH Group Donors; C506665:histamine dehydrogenase; D015232:Dinoprostone