首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Post-receptorial mechanisms underlie functional disregulation of beta(2)-adrenergic receptors in lymphocytes from Multiple Sclerosis patients.
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Post-receptorial mechanisms underlie functional disregulation of beta(2)-adrenergic receptors in lymphocytes from Multiple Sclerosis patients.

机译:受体后机制是多发性硬化症患者淋巴细胞中β(2)-肾上腺素能受体功能失调的基础。

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Increased density of beta(2)-adrenergic receptors has been demonstrated on peripheral blood mononuclear cells (PBMCs) from Multiple Sclerosis (MS) patients. In this study we found that isoproterenol reduces T-cell proliferation and IFNgamma secretion in PBMCs cultures from healthy controls and IFNbeta-treated but not untreated MS patients. Reduced expression levels of G protein coupled receptor kinase (GRK)2/3 (p<0.05) and increased isoproterenol-induced cAMP accumulation (p<0.0001) were found in PBMCs from all MS patients. Dibutyryl cAMP reduced the proliferation of PBMCs from all subgroups but in a slighter manner in untreated MS patients. We conclude that signalling through beta(2)-adrenergic receptors is chronically up-regulated but functionally uncoupled to immunoregulatory functions of lymphocytes from MS patients. Disregulation downstream the cAMP-associated signalling may underlie such a phenomenon.
机译:在多发性硬化症(MS)患者的外周血单核细胞(PBMC)上已证明增加的β(2)-肾上腺素受体密度。在这项研究中,我们发现异丙肾上腺素可减少健康对照和IFNbeta治疗但未治疗的MS患者的PBMC培养物中的T细胞增殖和IFNγ分泌。在所有MS患者的PBMC中,发现G蛋白偶联受体激酶(GRK)2/3的表达水平降低(p <0.05),异丙肾上腺素诱导的cAMP积累增加(p <0.0001)。 Dibutyryl cAMP降低了所有亚组的PBMC的增殖,但在未经治疗的MS患者中则稍有减少。我们得出结论,通过β(2)-肾上腺素受体的信号传导是慢性上调的,但功能上与MS患者淋巴细胞的免疫调节功能不相关。这种现象可能是下游与cAMP相关信号的失调所致。

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