title: Patented natural avocado sugar modulates the HBD-2 and HBD-3 expression in human keratinocytes through toll-like receptor-2 and ERK/MAPK activation.
abstract: Keratinocytes stimulated by microbial organisms secrete not only a variety of cytokines, chemokines and growth factors, but also antimicrobial peptides such as beta-defensins (HBDs) such as HBD-2 and HBD-3. AV119, a patented blend of avocado sugar, triggers the up-regulation of HBD-2 in skin epithelia upon contact with AV119, but the signalling mechanisms involved are not completely understood. The purpose of this study was to determine if AV119 was able to induce also the expression of HBD-3 in human keratinocytes. In addition, the receptor and intracellular pathways involved in the AV119 up-regulation of HBD-2 and HBD-3 were investigated. Our results demonstrated that AV119 induces a significantly increase of the expression of HBD-3. In addition, the HBD-2 and HBD-3 AV119-induced gene expression and release are TLR-2 dependent. Finally, we demonstrated that AV119 induced ERK/MAPK phosphorylation in human keratinocytes, thus providing evidence that HBD-2 and HBD-3 secretion is through the same transductional pathway. The ability of AV119 to induce also HBD-3 may amplify its therapeutic potential against a broader spectrum of bacterial and yeast strains responsible for human skin disorders.
authors.affiliation: Section of Microbiology and Clinical Microbiology, Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Iole
authors.initials: I
authors.lastname: Paoletti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Buommino
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fusco
authors.forename: Caroline
authors.initials: C
authors.lastname: Baudouin
authors.forename: Philippe
authors.initials: P
authors.lastname: Msika
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Tufano
authors.forename: Adone
authors.initials: A
authors.lastname: Baroni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Donnarumma
mesh_terms: D002241:Carbohydrates / Q000494:pharmacology*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D027421:Persea / Q000737:chemistry*; D010766:Phosphorylation / Q000187:drug effects; D000073893:Sugars; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D015854:Up-Regulation; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
chemical_list: C549768:AV119; D002241:Carbohydrates; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D000073893:Sugars; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D023083:beta-Defensins; D048049:Extracellular Signal-Regulated MAP Kinases