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- Title
Histamine Induces Cyclooxygenase (COX)-2 Expression and Prostaglandin I2 (PGI2) Production in Human Coronary Artery Endothelial Cells (HCAEC) via H-I Receptors (H1R) involving MAP Kinase p38 Activation.
- Authors
Xiaoyu Tan; Stechschulte, Daniel J.; Dileepan, Kottarappat N.
- Abstract
Histamine (HIS) is known to regulate vasodilation and endothelial cell inflammatory responses. COX-1 and COX-2 are rate-limiting enzymes involved in the biosyntheses of prostanoids including PGI2 and thromboxane A2 (TXA2). Since PGI2 is a vasodilator and TXA2 is a vasoconstrictor, their relative levels are critical for the maintenance of vascular tone. Although HIS is a potent vasodilator, its role in the regulation of the expression of COX-1 and COX-2 and production of PGI2 and TXA2 in HCAEC is not known. HCAEC monolayers were incubated with 1 to 100 µM HIS and the expression of COX-1 and COX-2 were analyzed by Real-Time PCR and Western blots. The effect of HIS on the production of PGI2 and TXA2 in resting and LPS-activated HCAEC were monitored by EIA. Incubation of HCAEC with HIS resulted in marked increase in COX-2 mRNA and protein expression with no change in COX-1 expression. Stimulation of HCAEC with HIS (1 to 100 µM) increased synthesis of PGI2 in time and dose-dependent fashion. HIS (10 µM) was also found to amplify LPS- induced PGI2 production by 4 to 6-fold. In contrast, HIS did not modulate TXA2 production in unactivated or LPS-treated HCAEC. HIS-induced COX-2 expression and PGI2 production were inhibited by H1R antagonist, diphenhydramine, but not by H2R antagonist, famotidine. Preincubation of HCAEC with p38 inhibitor but not JNK inhibitor abrogated HIS-induced COX-2 expression and PGI2 production. These results suggest a novel regulatory role for HIS in COX-2 expression and PGI2 synthesis in HCAEC.
- Subjects
HISTAMINE; CYCLOOXYGENASE 2; PROSTAGLANDINS; CELLS; CELL receptors; MITOGEN-activated protein kinases
- Publication
FASEB Journal, 2007, Vol 21, Issue 5, pA183
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.5.a183