TY - JOUR
T1 - Corticotropin releasing factor modulates interleukin-1-induced prostaglandin synthesis in fibroblasts
T2 - receptor binding and effects of antagonists
AU - Fleisher-Berkovich, Sigal
AU - Rimon, Gilad
AU - Danon, Abraham
N1 - Funding Information:
We wish to thank Dr. Jean Rivier for kindly providing d -PheCRF 12–41 and Dr. Richard Chizzonite, Hoffmann–La Roche, for the generous gift of IL-1α. This work was supported in part by a grant (to A.D.) from the Chief Scientist's Office, Ministry of Health, Israel.
PY - 1998/10/16
Y1 - 1998/10/16
N2 - Corticotropin releasing factor (CRF) is a predominant regulator of the neuroendocrine, autonomic and behavioral responses to stress. In addition, numerous studies support autocrine/paracrine roles for this peptide at peripheral sites. CRF and CRF binding sites have been identified in different regions of the central nervous system as well as in the heart, spleen, adrenal and testis, and high levels of CRF were detected in inflamed fibroblasts. However, the precise physiological or pathophysiological role of peripheral CRF cannot yet be discerned. Here we show that CRF, through interaction with specific membrane receptors, blocks the interleukin-1α (IL-1α)-stimulated prostaglandin (PG) synthesis in fibroblasts. Binding of [125I]-labeled CRF in fibroblasts was saturable and fitted a two sites model. K(D) for the higher-affinity class of receptors was 20±2.2 pM, and B(max) 1.95±0.22 fmol/mg protein. For the lower-affinity class of receptors K(D) was 160±17 nM, and B(max) 2.38±0.27 fmol/mg protein. CRF blocked the effect of IL-1α on PGE2 synthesis, and this was antagonised by D-PheCRF12-41. In addition, the CRF receptor antagonists α helical CRF9-41 and D-PheCRF12-41 at high concentrations inhibited the IL-1α-induced PG synthesis similarly to CRF, suggesting partial agonistic action. Taken together, these results suggest a modulatory role of CRF in inflammation. Copyright (C) 1998 Elsevier Science B.V.
AB - Corticotropin releasing factor (CRF) is a predominant regulator of the neuroendocrine, autonomic and behavioral responses to stress. In addition, numerous studies support autocrine/paracrine roles for this peptide at peripheral sites. CRF and CRF binding sites have been identified in different regions of the central nervous system as well as in the heart, spleen, adrenal and testis, and high levels of CRF were detected in inflamed fibroblasts. However, the precise physiological or pathophysiological role of peripheral CRF cannot yet be discerned. Here we show that CRF, through interaction with specific membrane receptors, blocks the interleukin-1α (IL-1α)-stimulated prostaglandin (PG) synthesis in fibroblasts. Binding of [125I]-labeled CRF in fibroblasts was saturable and fitted a two sites model. K(D) for the higher-affinity class of receptors was 20±2.2 pM, and B(max) 1.95±0.22 fmol/mg protein. For the lower-affinity class of receptors K(D) was 160±17 nM, and B(max) 2.38±0.27 fmol/mg protein. CRF blocked the effect of IL-1α on PGE2 synthesis, and this was antagonised by D-PheCRF12-41. In addition, the CRF receptor antagonists α helical CRF9-41 and D-PheCRF12-41 at high concentrations inhibited the IL-1α-induced PG synthesis similarly to CRF, suggesting partial agonistic action. Taken together, these results suggest a modulatory role of CRF in inflammation. Copyright (C) 1998 Elsevier Science B.V.
KW - D-PheCRF
KW - Inflammation
KW - Interleukin-1
KW - α Helical CRF
UR - http://www.scopus.com/inward/record.url?scp=0032538351&partnerID=8YFLogxK
U2 - 10.1016/S0167-0115(98)00107-4
DO - 10.1016/S0167-0115(98)00107-4
M3 - Article
AN - SCOPUS:0032538351
SN - 0167-0115
VL - 77
SP - 121
EP - 126
JO - Regulatory Peptides
JF - Regulatory Peptides
IS - 1-3
ER -