title: Stimulation of TLRs by LMW-HA induces self-defense mechanisms in vaginal epithelium.
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.
authors.affiliation: iMIL, italian Mucosal Immunity Laboratory, Dipartimento di Morfologia Umana e Scienze Biomediche Città Studi, Università degli Studi di Milano, Milano, Italy.
authors.forename: Giuseppina F
authors.initials: GF
authors.lastname: Dusio
authors.forename: Diego
authors.initials: D
authors.lastname: Cardani
authors.forename: Laura
authors.initials: L
authors.lastname: Zanobbio
authors.forename: Martina
authors.initials: M
authors.lastname: Mantovani
authors.forename: Patrizia
authors.initials: P
authors.lastname: Luchini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Battini
authors.forename: Valentina
authors.initials: V
authors.lastname: Galli
authors.forename: Angela
authors.initials: A
authors.lastname: Diana
authors.forename: Andrea
authors.initials: A
authors.lastname: Balsari
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D019848:Gene Expression Regulation, Archaeal / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism / Q000494:pharmacology*; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008024:Ligands; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014621:Vagina / Q000187:drug effects* / Q000276:immunology*; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; C106641:DEFB4A protein, human; D007155:Immunologic Factors; D018836:Inflammation Mediators; D008024:Ligands; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D023083:beta-Defensins; D006820:Hyaluronic Acid; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt