Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS

Cory Teuscher, Meena Subramanian, Rajkumar Noubade, Feng Gao Jian, Halina Offner, James F. Zachary, Elizabeth P. Blankenhorn

Research output: Contribution to journalArticle

70 Citations (Scopus)

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 H 4. 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.

Original languageEnglish (US)
Pages (from-to)10146-10151
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number24
DOIs
StatePublished - Jun 12 2007
Externally publishedYes

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Histamine H3 Receptors
Histamine
Autoimmune Diseases
Multiple Sclerosis
Histamine H1 Receptors
Histamine H2 Receptors
Biogenic Amines
Wild Animals
Autoimmune Experimental Encephalomyelitis
G-Protein-Coupled Receptors
Blood-Brain Barrier
Nervous System
Disease Progression
Permeability
Pharmacology
T-Lymphocytes

Keywords

  • Blood-brain barrier
  • Experimental allergic encephalomyelitis
  • Multiple sclerosis

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS. / Teuscher, Cory; Subramanian, Meena; Noubade, Rajkumar; Jian, Feng Gao; Offner, Halina; Zachary, James F.; Blankenhorn, Elizabeth P.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 24, 12.06.2007, p. 10146-10151.

Research output: Contribution to journalArticle

Teuscher, Cory ; Subramanian, Meena ; Noubade, Rajkumar ; Jian, Feng Gao ; Offner, Halina ; Zachary, James F. ; Blankenhorn, Elizabeth P. / Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS. In: Proceedings of the National Academy of Sciences of the United States of America. 2007 ; Vol. 104, No. 24. pp. 10146-10151.
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