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首页> 外文期刊>Clinical & developmental immunology. >Altered Sympathetic-to-Immune Cell Signaling via β 2 -Adrenergic Receptors in Adjuvant Arthritis
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Altered Sympathetic-to-Immune Cell Signaling via β 2 -Adrenergic Receptors in Adjuvant Arthritis

机译：通过 β 2 -肾上腺素受体改变交感-免疫细胞信号佐剂性关节炎

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Adjuvant-induced arthritic (AA) differentially affects norepinephrine concentrations in immune organs, and in vivo β -adrenergic receptor ( β -AR) agonist treatment distinctly regulates ex vivo cytokine profiles in different immune organs. We examined the contribution of altered β -AR functioning in AA to understand these disparate findings. Twenty-one or 28 days after disease induction, we examined β _(2)-AR expression in spleen and draining lymph nodes (DLNs) for the arthritic limbs using radioligand binding and western blots and splenocyte β -AR-stimulated cAMP production using enzyme-linked immunoassay (EIA). During severe disease, β -AR agonists failed to induce splenocyte cAMP production, and β -AR affinity and density declined, indicating receptor desensitization and downregulation. Splenocyte β _(2)-AR phosphorylation (p β _(2)-AR) by protein kinase A (p β _(2)-AR_(PKA)) decreased in severe disease, and p β _(2)-AR by G protein-coupled receptor kinases (p β _(2)-AR_(GRK)) increased in chronic disease. Conversely, in DLN cells, p β _(2)-AR_(PKA)rose during severe disease, but fell during chronic disease, and p β _(2)-AR_(GRK)increased during both disease stages. A similar p β _(2)-AR pattern in DLN cells with the mycobacterial cell wall component of complete Freund's adjuvant suggests that pattern recognition receptors (i.e., toll-like receptors) are important for DLN p β _(2)-AR patterns. Collectively, our findings indicate lymphoid organ- and disease stage-specific sympathetic dysregulation, possibly explaining immune compartment-specific differences in β _(2)-AR-mediated regulation of cytokine production in AA and rheumatoid arthritis.
机译：佐剂诱导的关节炎（AA）会不同地影响免疫器官中去甲肾上腺素的浓度，体内β-肾上腺素能受体（β-AR）激动剂治疗可明显调节不同免疫器官中的离体细胞因子谱。我们研究了AA中β-AR功能改变的作用，以了解这些不同的发现。疾病诱导后的二十一或二十八天，我们使用放射性配体结合和Western印迹法以及脾细胞检查了脾肢和引流淋巴结（DLN）中β_（2）-AR的表达以及脾细胞中β-AR刺激酶的cAMP产生连锁免疫分析（EIA）。在严重疾病期间，β-AR激动剂不能诱导脾细胞cAMP的产生，β-AR亲和力和密度下降，表明受体脱敏和下调。在严重疾病中，蛋白激酶A（pβ_（2）-AR_（PKA））引起的脾细胞β_（2）-AR磷酸化（pβ_（2）-AR）降低，pβ_（2）-AR降低在慢性疾病中，G蛋白偶联受体激酶（pβ_（2）-AR_（GRK））升高。相反，在DLN细胞中，pβ_（2）-AR_（PKA）在严重疾病期间升高，但在慢性疾病期间下降，并且pβ_（2）-AR_（GRK）在两个疾病阶段均升高。具有完全弗氏佐剂的分枝杆菌细胞壁成分的DLN细胞中类似的pβ_（2）-AR模式表明，模式识别受体（即toll样受体）对于DLN pβ_（2）-AR模式很重要。总的来说，我们的发现表明淋巴器官和疾病阶段特定的交感神经失调，可能解释了免疫球蛋白特异性的差异，在AA和类风湿性关节炎的β_（2）-AR介导的细胞因子生产调控中。

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