Effect of corticotropin-releasing factor on prostaglandin synthesis in endothelial cells and fibroblasts.
Recent evidence suggests that not only the end product of the hypothalamic-pituitary-adrenal axis, but also other hormones in the axis may be involved in regulation of the inflammatory response. We investigated the role of CRF in the regulation of prostaglandin (PG) synthesis in fibroblasts and endothelial cells. Recombinant human interleukin-1 alpha (IL-1 alpha) increased prostacyclin synthesis in endothelial cells by 66% and prostaglandin E2 (PGE2) synthesis in fibroblasts by 91%. The PG response to IL-1 alpha was suppressed to about 50% by simultaneous addition of CRF in endothelial cells (75.6 +/- 6.2 vs. 159.7 +/- 14.9 ng 6-keto-PGF1 alpha/mg protein) and fibroblasts (115.5 +/- 23 vs. 233.6 +/- 42 ng PGE2/mg protein). IL-1 alpha enhanced phospholipase A2 activity by 30% and prostaglandin H synthase activity by 60%, and the two effects were completely blocked by CRF. It is concluded that CRF suppresses IL-1 alpha-induced PG synthesis through actions on both phospholipase A2 and cyclooxygenase. In view of the essential role of central PGE2 in IL-1 alpha-induced CRF/ACTH release, these findings suggest a novel regulatory cascade in immune-neuroendocrine interactions.
Fleisher-Berkovich
S
S
Department of Clinical Pharmacology, Corob Center of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.
Danon
A
A
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism / Q000502:physiology; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology; D011453:Prostaglandins / Q000096:biosynthesis*
D007375:Interleukin-1; D011453:Prostaglandins; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone