Minocycline down-regulates topical mucosal inflammation during the application of microbicide candidates.

Minocycline down-regulates topical mucosal inflammation during the application of microbicide candidates.
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米诺环素在使用候选杀菌剂期间下调局部粘膜炎症

DOI:
10.1371/journal.pone.0043211
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Zhang X
Zhang X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li L;Ben Y;Zhu Z;Li W;Xu J;Zhang X

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一种有效的抗人类免疫缺陷病毒-1(HIV-1)杀微生物剂应在不引起局部免疫异常激活的情况下发挥作用,这将增加艾滋病毒感染的风险。在本研究中,我们证明了阴道应用硫酸纤维素(CS)凝胶可引起局部粘膜炎症反应;在CS凝胶中加入米诺环素可显著减轻小鼠模型的炎症反应。CS联合米诺环素不仅能减少宫颈阴道灌洗液(CVL)中炎性细胞因子的产生,还能下调CD_4~+T细胞的活化和包括HIV靶细胞在内的其他免疫细胞向阴道组织的募集。此外,体外HIV-1假病毒感染抑制实验表明,与单独使用CS凝胶相比,复合凝胶对不同亚型HIV-1伪病毒的感染效率降低。这些结果表明,米诺环素可以整合到杀微生物剂的制剂中,以抑制局部黏膜免疫的异常激活,并在使用杀微生物剂的过程中提高安全性。
An effective anti-human immunodeficiency virus-1 (HIV-1) microbicide should exert its action in the absence of causing aberrant activation of topical immunity that will increase the risk of HIV acquisition. In the present study, we demonstrated that the vaginal application of cellulose sulfate (CS) gel induced topical mucosal inflammatory responses; the addition of minocycline to CS gel could significantly attenuate the inflammation in a mice model. The combined gel of CS plus minocycline not only reduced the production of inflammatory cytokines in cervicovaginal lavages (CVLs), also down-regulated the activation of CD4+ T cells and the recruitment of other immune cells including HIV target cells into vaginal tissues. Furthermore, an In vitro HIV-1 pseudovirus infection inhibition assay showed that the combined gel decreased the infection efficacy of different subtypes of HIV-1 pseudoviruses compared with that of CS gel alone. These results implicate that minocycline could be integrated into microbicide formulation to suppress the aberrant activation of topical mucosal immunity and enhance the safety profile during the application of microbicides.
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