Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium
Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium
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DOI：
10.1038/icb.2010.140
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发表时间：
2011-07-01
影响因子：
4
通讯作者：
Rumio, Cristiano
中科院分区：
文献类型：
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作者：
Dusio, Giuseppina F.;Cardani, Diego;Rumio, Cristiano
先天免疫系统存在于整个女性生殖道，并与适应性免疫系统同步发挥作用，以提高胎儿生存机会的方式提供保护，同时保护胎儿免受潜在病原体的侵害。最近的研究表明，低分子量透明质酸（lw - ha）激活表皮中toll样受体（TLR）2和4可诱导抗菌肽β -防御素2的分泌。在本研究中，我们发现LMW-HA通过激活TLR2和TLR4诱导阴道上皮细胞释放不同的抗菌肽。此外，我们发现LMW-HA有利于阴道上皮损伤的修复，涉及TLR2和TLR4，并且独立于其经典受体CD44。这种低分子量ha的伤口愈合活性依赖于Akt/磷脂酰肌醇3激酶途径。因此，这些研究结果表明，阴道上皮不仅仅是一个简单的物理屏障，以防止入侵的病原体：相反，这一表面作为先天宿主防御的有效参与者，这可能会调节其抗菌特性和损伤恢复活性，在低分子量血凝素刺激；这种活性可能为这种高度和持续暴露于微生物群的身体隔室提供额外的保护活性，改善阴道上皮在基础和病理条件下的自卫能力。免疫学与细胞生物学（2011）89,630-639；doi: 10.1038 / icb.2010.140;2010年11月23日在线发布
The innate immune system is present throughout the female reproductive tract and functions in synchrony with the adaptive immune system to provide protection in a way that enhances the chances for fetal survival, while protecting against potential pathogens. Recent data show that activation of Toll-like receptor (TLR)2 and 4 by low-molecular weight hyaluronic acid (LMW-HA) in the epidermis induces secretion of the antimicrobial peptide beta-defensin 2. In the present work, we show that LMW-HA induces vaginal epithelial cells to release different antimicrobial peptides, via activation of TLR2 and TLR4. Further, we found that LMW-HA favors repair of vaginal epithelial injury, involving TLR2 and TLR4, and independently from its classical receptor CD44. This wound-healing activity of LMW-HA is dependent from an Akt/phosphatidylinositol 3 kinase pathway. Therefore, these findings suggest that the vaginal epithelium is more than a simple physical barrier to protect against invading pathogens: on the contrary, this surface acts as efficient player of innate host defense, which may modulate its antimicrobial properties and injury restitution activity, following LMW-HA stimulation; this activity may furnish an additional protective activity to this body compartment, highly and constantly exposed to microbiota, ameliorating the self-defense of the vaginal epithelium in both basal and pathological conditions. Immunology and Cell Biology (2011) 89, 630-639; doi:10.1038/icb.2010.140; published online 23 November 2010