Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium |
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Authors: | Dusio Giuseppina F Cardani Diego Zanobbio Laura Mantovani Martina Luchini Patrizia Battini Lorenzo Galli Valentina Diana Angela Balsari Andrea Rumio Cristiano |
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Affiliation: | iMIL, italian Mucosal Immunity Laboratory, Dipartimento di Morfologia Umana e Scienze Biomediche Città Studi, Università degli Studi di Milano, Milano, Italy. |
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Abstract: | 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 β-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. |
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