title: Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS.
abstract: Histamine (HA), a biogenic amine with a broad spectrum of activities in both physiological and pathological settings, plays a key regulatory role in experimental allergic encephalomyelitis, the autoimmune model of multiple sclerosis. HA exerts its effect through four G protein-coupled receptors designated HA receptor H1, H2, H3, and H4. We report here that, compared with wild-type animals, mice with a disrupted HA H3 receptor (H3RKO), the expression of which is normally confined to cells of the nervous system, develop more severe disease and neuroinflammation. We show that this effect is associated with dysregulation of blood-brain barrier permeability and increased expression of MIP-2, IP-10, and CXCR3 by peripheral T cells. Our data suggest that pharmacological targeting of the H3R may be useful in preventing the development and formation of new lesions in multiple sclerosis, thereby significantly limiting the progression of the disease.
authors.affiliation: Departments of Medicine and Pathology, University of Vermont, Burlington, VT 05405, USA. c.teuscher@uvm.edu
authors.forename: Cory
authors.initials: C
authors.lastname: Teuscher
authors.forename: Meena
authors.initials: M
authors.lastname: Subramanian
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Noubade
authors.forename: Jian Feng
authors.initials: JF
authors.lastname: Gao
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
authors.forename: James F
authors.initials: JF
authors.lastname: Zachary
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Blankenhorn
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D004198:Disease Susceptibility / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D018448:Models, Immunological; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018100:Receptors, Histamine H3