TY - JOUR
T1 - Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS
AU - Teuscher, Cory
AU - Subramanian, Meena
AU - Noubade, Rajkumar
AU - Jian, Feng Gao
AU - Offner, Halina
AU - Zachary, James F.
AU - Blankenhorn, Elizabeth P.
PY - 2007/6/12
Y1 - 2007/6/12
N2 - 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.
AB - 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.
KW - Blood-brain barrier
KW - Experimental allergic encephalomyelitis
KW - Multiple sclerosis
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U2 - 10.1073/pnas.0702291104
DO - 10.1073/pnas.0702291104
M3 - Article
C2 - 17548817
AN - SCOPUS:34547142877
SN - 0027-8424
VL - 104
SP - 10146
EP - 10151
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 24
ER -