Effects of corticotropin-releasing hormone (CRH) on monocyte function, mediated by CRH-receptor subtype R1 and R2: a potential link between mood disorders and endothelial dysfunction?
Psychosocial factors have been reported to be independently associated with coronary heart disease (CHD). Though corticotropin-releasing hormone (CRH) is the major hormone activated during adaptive responses to stressful stimuli, the undergoing pathophysiological mechanism related to stress-induced endothelial dysfunction is still poorly understood. This study sought to investigate the effects of extrahypothalamic CRH on monocyte/endothelium adhesion. Second we elucidate the influence of CRH on monocytic endothelin-1 (ET-1) and nitric oxide (NO) release and the receptors involved. Cell adhesion was determined using an adhesion assay, MAC-1 expression by flow cytometry. ET-1/NO release were quantified via ELISA or fluorometrically, monocytic CRH-receptors were confirmed by mRNA. Corticotropin-releasing hormone induced a significant time- and concentration-dependent increase of cell adhesion as well as monocytic MAC-1 expression; endothelial ICAM-1 and VCAM-1 expression was not altered. In addition, corticotropin-releasing hormone significantly increased monocytic ET-1 release whereas nitric oxide release was decreased. The effect was abolished by the selective CRH-receptor antagonist astressin. Our findings support the importance of peripherally circulating corticotropin-releasing hormones, by influencing specific homeostatic properties of monocytes. Our data may provide a novel concept of how specific CRH-receptor antagonists may prevent CRH (stress)-related endothelial dysfunction up to cardiovascular complications.
Wilbert-Lampen
Ute
U
Medizinische Klinik und Poliklinik I, Klinikum Grosshadern, Ludwig-Maximillian-Universität, München, Germany. uwilbert@med.uni-muenchen.de
Straube
Florian
F
Trapp
Anja
A
Deutschmann
Agnieszka
A
Plasse
Andrea
A
Steinbeck
Gerhard
G
D039481:CD11b Antigen / Q000032:analysis; D002448:Cell Adhesion; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000502:physiology*; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D019964:Mood Disorders / Q000209:etiology*; D009569:Nitric Oxide / Q000378:metabolism; D018019:Receptors, Corticotropin-Releasing Hormone / Q000145:classification / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis
D039481:CD11b Antigen; D019332:Endothelin-1; D018019:Receptors, Corticotropin-Releasing Hormone; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D003346:Corticotropin-Releasing Hormone