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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes.
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Regulation of CCR5 and CXCR4 expression by type 1 and type 2 cytokines: CCR5 expression is downregulated by IL-10 in CD4-positive lymphocytes.

机译：1型和2型细胞因子对CCR5和CXCR4表达的调节：IL-10在CD4阳性淋巴细胞中下调CCR5表达。

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摘要

HIV-1 transmission and disease progression is, in general, characterized by initial predominance of macrophage tropic, non-syncytium-inducing strains followed by a switch to T-cell tropic, syncytium-inducing strains. Using sensitive, quantitative kinetic RT-PCR, we examined cytokine regulation of tropism-specific HIV-1 coreceptor expression in PBMCs from HIV-1-seronegative individuals. Proinflammatory (TNF-alpha and IL-12) and type 1 cytokines (IFN-gamma and IL-2) significantly upregulated CCR5 (wt allele) mRNA expression in CCR5 homozygous wild-type (wt/wt) and heterozygous individuals (wt/del) (P < 0.02). CCR5 (wt) mRNA expression in unstimulated PBMCs was significantly increased in wt/wt individuals compared to that of wt/del individuals (P < 0.01). In wt/del individuals, del CCR5 mRNA was expressed at 10-fold greater levels than wt CCR5 mRNA in unstimulated PBMCs from the same individual. Flow cytometry confirmed that upregulated CCR5 mRNA following type 1 cytokine stimulation leads to increased cell surface expression of CCR5 protein. The type 2 cytokine IL-10 downregulated both CCR5 mRNA and protein expression in wt/wt and wt/del individuals. Proinflammatory, type 1, and type 2 cytokines significantly increased CXCR4 mRNA expression in wt/wt, wt/del, and del/del CCR5 genotypes (P < 0.02). These results suggest that changes in the cytokine milieu influence chemokine receptor expression and may explain emergence of tropism-specific strains facilitating HIV transmission and disease progression.
机译：通常，HIV-1传播和疾病进展的特征是最初主要是巨噬细胞嗜性，非合胞体诱导型菌株，然后转向T细胞嗜性，合胞体诱导型菌株。使用敏感的，定量的动力学RT-PCR，我们检查了HIV-1血清阴性个体的PBMC中嗜性特异性HIV-1共受体表达的细胞因子调节。在CCR5纯合野生型（wt / wt）和杂合个体（wt / del）中，促炎性（TNF-alpha和IL-12）和1型细胞因子（IFN-γ和IL-2）显着上调了CCR5（wt等位基因）mRNA表达。 ）（P <0.02）。与wt / del个体相比，wt / wt个体中未刺激的PBMC中CCR5（wt）mRNA表达显着增加（P <0.01）。在wt / del个体中，在同一个体的未刺激PBMC中，del CCR5 mRNA的表达水平比wt CCR5 mRNA高10倍。流式细胞仪证实1型细胞因子刺激后CCR5 mRNA上调导致CCR5蛋白在细胞表面表达增加。 2型细胞因子IL-10下调wt / wt和wt / del个体的CCR5 mRNA和蛋白表达。在wt / wt，wt / del和del / del CCR5基因型中，促炎1型和2型细胞因子显着提高了CXCR4 mRNA的表达（P <0.02）。这些结果表明，细胞因子环境的变化会影响趋化因子受体的表达，并可能解释了向性特异性菌株的出现，这些菌株促进了HIV的传播和疾病的发展。

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