title: Neurotensin and CRH interactions augment human mast cell activation.
abstract: Stress affects immunity, but the mechanism is not known. Neurotensin (NT) and corticotropin-releasing hormone (CRH) are secreted under stress in various tissues, and have immunomodulatory actions. We had previously shown that NT augments the ability of CRH to increase mast cell-dependent skin vascular permeability in rodents. Here we show that NT triggered human mast cell degranulation and significantly augmented CRH-induced vascular endothelial growth factor (VEGF) release. Investigation of various signaling molecules indicated that only NF-κB activation was involved. These effects were blocked by pretreatment with the NTR antagonist SR48692. NT induced expression of CRH receptor-1 (CRHR-1), as shown by Western blot and FACS analysis. Interestingly, CRH also induced NTR gene and protein expression. These results indicate unique interactions among NT, CRH, and mast cells that may contribute to auto-immune and inflammatory diseases that worsen with stress.
authors.affiliation: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Konstantinos-Dionysios
authors.initials: KD
authors.lastname: Alysandratos
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Asadi
authors.forename: Asimenia
authors.initials: A
authors.lastname: Angelidou
authors.forename: Bodi
authors.initials: B
authors.lastname: Zhang
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Sismanopoulos
authors.forename: Hailing
authors.initials: H
authors.lastname: Yang
authors.forename: Agatha
authors.initials: A
authors.lastname: Critchfield
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D015550:Cell Degranulation / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009496:Neurotensin / Q000494:pharmacology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D018019:Receptors, Corticotropin-Releasing Hormone; D018028:Receptors, Neurotensin; D042461:Vascular Endothelial Growth Factor A; D009496:Neurotensin; D003346:Corticotropin-Releasing Hormone