Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract
Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract
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DOI：
10.1111/j.1365-2567.2009.03165.x
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发表时间：
2010-02-01
期刊：
影响因子：
6.4
通讯作者：
Wira, Charles R.
中科院分区：
文献类型：
--
作者：
Ghosh, Mimi;Shen, Zheng;Wira, Charles R.
Trappin-2/Elafin是一种丝氨酸蛋白酶抑制剂，作为粘膜表面的抗炎介质发挥重要作用。此外，Trappin-2/Elafin对革兰氏阳性和革兰氏阴性细菌和真菌病原体具有抗菌活性。在这项研究中，我们研究了生产的Trappin-2/Elafin上皮细胞从人类上下女性生殖道，以及其作为一种抗人类免疫缺陷病毒（HIV）-1分子的活性。我们发现，原代子宫，输卵管，宫颈和子宫颈外上皮细胞产生Trappin-2/Elafin组成和生产的Trappin-2/Elafin增强后，刺激与聚（I：C），特别是子宫细胞。鉴于Trappin-2/Elafin在生殖道中的存在，我们测试了重组Trappin-2/Elafin抑制HIV-1（一种重要的性传播病原体）的能力。我们发现重组Trappin-2/Elafin能够以剂量依赖的方式抑制T细胞嗜性X4/IIIB和巨噬细胞嗜性R5/BaL HIV-1。当病毒与Trappin-2/Elafin孵育时观察到抑制活性，但当Trappin-2/Elafin在感染前或感染后加入细胞时则没有。这表明抑制机制可能是HIV-1和Trappin-2/Elafin之间的直接相互作用。此外，我们测量了HIV阳性和HIV阴性女性宫颈阴道灌洗液（CVL）中分泌的Trappin-2/Elafin的水平，发现HIV阴性女性CVL中分泌的Trappin-2/Elafin的平均水平较高，尽管这些值没有达到统计学显著性。我们还发现，女性在月经周期的分泌期产生更多的Trappin-2/Elafin在CVL相对于女性在月经周期的增殖期。我们的数据表明，Trappin-2/Elafin可能是一种重要的内源性杀微生物剂的女性生殖道，是对HIV-1的保护。
P>Trappin-2/Elafin is a serine protease inhibitor that plays a major role as an anti-inflammatory mediator at mucosal surfaces. In addition, Trappin-2/Elafin has antibacterial activity against Gram-positive and Gram-negative bacterial and fungal pathogens. In this study we examined the production of Trappin-2/Elafin by epithelial cells from the human upper and lower female reproductive tract as well as its activity as an anti-human immunodeficiency virus (HIV)-1 molecule. We found that primary uterine, Fallopian tube, cervical and ectocervical epithelial cells produce Trappin-2/Elafin constitutively and that production of Trappin-2/Elafin is enhanced following stimulation with Poly(I:C), especially by the uterine cells. Given the presence of Trappin-2/Elafin in the reproductive tract, we tested the ability of recombinant Trappin-2/Elafin to inhibit HIV-1, an important sexually transmitted pathogen. We found that recombinant Trappin-2/Elafin was able to inhibit both T-cell-tropic X4/IIIB and macrophage-tropic R5/BaL HIV-1 in a dose-dependent manner. The inhibitory activity was observed when virus was incubated with Trappin-2/Elafin but not when Trappin-2/Elafin was added to cells either before infection or after infection. This suggests that the mechanism of inhibition is likely to be a direct interaction between HIV-1 and Trappin-2/Elafin. Additionally, we measured the levels of secreted Trappin-2/Elafin in cervico-vaginal lavages (CVL) from both HIV-positive and HIV-negative women and found that average levels of secreted Trappin-2/Elafin were higher in the CVL from HIV-negative women, although the values did not reach statistical significance. We also found that women at the secretory phase of the menstrual cycle produced more Trappin-2/Elafin in CVL relative to women at the proliferative phase of the menstrual cycle. Our data suggest that Trappin-2/Elafin might be an important endogenous microbicide of the female reproductive tract that is protective against HIV-1.