IL-1alpha but not IL-1beta-induced prostaglandin synthesis is inhibited by corticotropin-releasing factor.
Interleukin (IL)-1alpha and IL-1beta share low amino acid homology, but exhibit a very similar array of biological activities. The authors previously showed negative regulation of IL-1alpha-induced prostaglandin (PG) production by corticotropin releasing factor (CRF). In this study, the authors compared the effect of CRF on IL-1alpha- and IL-1beta-induced PG synthesis. IL-1alpha (100 U/ml) increased prostacyclin (PGI2) (measured as 6-keto PGF1alpha[6K]) synthesis in endothelial cells and the production of PGE2in fibroblasts. The PG response to IL-1alpha was suppressed by simultaneous exposure to CRF (2.5x10(-11)-2.5x10(-8) M) in both cell types. IL-1alpha enhanced both phospholipase A2(PLA2) and prostaglandin H synthase (PGHS) activities, and the two effects were completely abrogated by CRF. IL- 1beta (100 U/ml) was as active as IL-1alpha in triggering release of PGI2 from endothelial cells and PGE2 from fibroblasts. However, CRF (2.5x10(-11)-2.5x10(-8) M) failed to alter the IL-1beta-induced PG synthesis in both cell types. Following IL-1beta PGHS activity, and to a lesser extent PLA2 activity, were enhanced, however CRF only inhibited PGHS and not PLA2 activity. It is concluded that although IL-1alpha and IL-1beta usually produce similar biological effects, here they seem to act via different mechanisms. The different regulation of IL-1alpha and IL-1beta pro-inflammatory activities by CRF may attribute special precision and specificity to the neuroendocrine-immune control of inflammatory processes.
Fleisher-Berkovich
S
S
Department of Clinical Pharmacology, The Corob Center of Health Sciences, Ben-Gurion University and Soroka Medical Center, Beer-Sheva, 84105, Israel.
Danon
A
A
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*
D007375:Interleukin-1; D011453:Prostaglandins; D003346:Corticotropin-Releasing Hormone; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone