Journal article
Central histamine [H.sub.3] receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS
Proceedings of the National Academy of Sciences - PNAS, Vol.104(24), p10146
12 Jun 2007
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 [H.sub.1], [H.sub.2], [H.sub.3], and [H.sub.4]. We report here that, compared with wild-type animals, mice with a disrupted HA [H.sub.3] 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 bloodbrain barrier permeability and increased expression of MIP-2, IP-10, and CXCR3 by peripheral T cells. Our data suggest that pharmacological targeting of the [H.sub.3]R may be useful in preventing the development and formation of new lesions in multiple sclerosis, thereby significantly limiting the progression of the disease. blood-brain barrier | experimental allergic encephalomyelitis | multiple sclerosis
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Details
- Title
- Central histamine [H.sub.3] receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS
- Creators
- Cory TeuscherMeena SubramanianRajkumar NoubadeJian Feng GaoHalina OffnerJames F ZacharyElizabeth P Blankenhorn
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.104(24), p10146
- Publisher
- National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019231641004721