CCL20/MIP3alpha is a novel anti-HIV-1 molecule of the human female reproductive tract.

CCL20/MIP3alpha is a novel anti-HIV-1 molecule of the human female reproductive tract.
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DOI:
10.1111/j.1600-0897.2009.00713.x
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发表时间:
2009-07
期刊:
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子:
--
通讯作者:
Wira CR
Wira CR
中科院分区:
其他
文献类型:
--
作者:
Ghosh M;Shen Z;Schaefer TM;Fahey JV;Gupta P;Wira CR

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CCL 20/MIP 3 α是一种未成熟树突状细胞的趋化因子,也是一种抗革兰氏阳性和革兰氏阴性细菌的抗菌剂。CCL 20/MIP 3 α作为抗病毒剂的作用尚不清楚。在这项研究中,我们检测了来自雌性上生殖道上皮细胞的CCL 20/MIP 3 α的产生以及其作为抗病毒分子的活性。用Poly(I:C)处理原代子宫和输卵管上皮细胞,通过Real-time RT-PCR和ELISA检测CCL 20/MIP 3 α mRNA和蛋白的表达。使用指示细胞系TZM-bl测定抗HIV活性,并使用光度计定量。原代子宫和输卵管上皮细胞组成性产生CCL 20/MIP 3 α,并且在用病毒双链RNA模拟物Poly(I:C)刺激后产生增强。重组CCL 20/MIP 3 α在感染前或感染后均不能抑制HIV-1的X4/IIIB和R5/BaL两种嗜T细胞的活性。这表明抑制机制可能是HIV-1与CCL 20/MIP 3 α之间的直接相互作用。本研究表明,CCL 20/MIP 3 α是女性生殖道重要的内源性抗HIV-1杀微生物剂。
CCL20/MIP3α is a chemokine for immature dendritic cells as well as an antibacterial against gram-positive and gram-negative bacteria. The role of CCL20/MIP3α as an antiviral is unknown. In this study, we have examined the production of CCL20/MIP3α by epithelial cells from the upper female reproductive tract as well as its activity as an antiviral molecule. Primary uterine and Fallopian tube epithelial cells were treated with Poly(I:C) and CCL20/MIP3α mRNA and protein was measured by Real-time RT-PCR and ELISA assays. Anti-HIV activity was determined using an indicator cell line TZM-bl and quantified by using a luminometer. Primary uterine and Fallopian tube epithelial cells produce CCL20/MIP3α constitutively and the production is enhanced following stimulation with viral double-stranded RNA mimic Poly(I:C). Recombinant CCL20/MIP3α was able to inhibit both T-cell-tropic X4/IIIB and macrophage-tropic R5/BaL HIV-1 when virus was directly incubated with CCL20/MIP3α but not when CCL20/MIP3α was added to cells either prior to infection or post-infection. This suggests that the mechanism of inhibition is likely to be a direct interaction between HIV-1 and CCL20/MIP3α. This study demonstrates that CCL20/MIP3α is an important endogenous anti-HIV-1 microbicide of the female reproductive tract.
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