title: Neuropeptide urocortin and its receptors are expressed in rat Kupffer cells.
abstract: The stress neuropeptides, corticotropin-releasing hormone (CRH) and urocortin (UCN), modulate the inflammatory response via the hypothalamus-pituitary-adrenal axis and locally, in a paracrine manner, act on mast and macrophage cells. Kupffer cells (KCs) are the resident macrophages of the liver. They represent the bulk of tissue macrophages in the body and they are the first to face invading noxious agents reaching the body via the portal circulation. The aim of the present report was to study the expression of the CRH system in rat KC and test its functionality. Our findings are as follows: (1) In highly purified KCs the transcripts of UCN, of its receptors CRHR1, CRHR2 and that of the pseudoreceptor CRH-binding protein (CRHBP) were present while that of CRH was not detectable. (2) Similarly, immunoreactive UCN, CRHR1, CRHR2 and CRHBP were easily detectable by immunohistochemistry and immunofluorescence in sections of whole rat liver (localized in KC) as well as in purified KC while CRH was again not detectable. (3) Exposure of purified KC to CRH or UCN suppressed lipopolysaccharide-induced tumor necrosis factor alpha production, an effect completely prevented by the CRHR1 and CRHR2 receptor antagonist astressin. Our data demonstrate the presence of UCN and its receptors in rat KC, the absence of CRH, and the functionality of these receptors. We propose that a UCN-based system may affect local inflammatory phenomena in the liver acting in a paracrine manner.
authors.affiliation: Department of Pharmacology, School of Medicine, University of Crete, Heraklion, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Charalampopoulos
authors.forename: Ariadne
authors.initials: A
authors.lastname: Androulidaki
authors.forename: Vassilis
authors.initials: V
authors.lastname: Minas
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Chatzaki
authors.forename: Chistos
authors.initials: C
authors.lastname: Tsatsanis
authors.forename: George
authors.initials: G
authors.lastname: Notas
authors.forename: Costas
authors.initials: C
authors.lastname: Xidakis
authors.forename: George
authors.initials: G
authors.lastname: Kolios
authors.forename: Elias
authors.initials: E
authors.lastname: Kouroumalis
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Margioris
authors.forename: Achille
authors.initials: A
authors.lastname: Gravanis
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D005786:Gene Expression Regulation; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D054832:Urocortins; D000099052:CRF Receptor, Type 1
chemical_list: C101531:CRF receptor type 2; D002352:Carrier Proteins; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D014409:Tumor Necrosis Factor-alpha; D054832:Urocortins; C067133:corticotropin releasing factor-binding protein; C104416:astressin; D000099052:CRF Receptor, Type 1; D003346:Corticotropin-Releasing Hormone