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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Central histamine H_3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS
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Central histamine H_3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS

机译：中枢组胺H_3受体信号负调节中枢神经系统自身免疫性炎症疾病的易感性

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摘要

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_1, H_2, H_3, and H_4. We report here that, compared with wild-type animals, mice with a disrupted HA H_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 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 H_3R may be useful in preventing the development and formation of new lesions in multiple sclerosis, thereby significantly limiting the progression of the disease.
机译：组胺（HA）是一种在生理和病理环境中均具有广泛活性的生物胺，它在实验性变应性脑脊髓炎（多发性硬化症的自身免疫模型）中起着关键的调节作用。 HA通过四个称为HA受体H_1，H_2，H_3和H_4的G蛋白偶联受体发挥作用。我们在这里报告，与野生型动物相比，具有受损的HA H_3受体（H3RKO）的小鼠发展为更严重的疾病和神经炎症，该小鼠的表达通常限于神经系统细胞。我们表明，这种作用与外周血T细胞的血脑屏障通透性失调和MIP-2，IP-10和CXCR3的表达增加有关。我们的数据表明，H_3R的药理靶向可能有助于预防多发性硬化症中新病灶的发展和形成，从而显着限制疾病的进展。

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