Patented natural avocado sugars modulate the HBD-2 expression in human keratinocytes through the involvement of protein kinase C and protein tyrosine kinases.
Skin keratinocytes constitute a protective mechanical barrier against invading microorganisms. Stimulated keratinocytes produce endogenous peptides such as the beta-defensins that have direct antimicrobial activity against a broad spectrum of pathogens, including most bacteria, certain fungi and enveloped viruses. In particular, human beta-defensin 2 (HBD-2) is virtually absent in normal skin and its expression in human keratinocytes requires stimulation by cytokines or bacteria. AV119, a patented avocado sugar, triggers the up-regulation of HBD-2, but the signalling mechanisms involved in this up-regulation in stimulated keratinocytes are not fully understood. In the present study, we examined the intracellular signalling pathways and nuclear responses in skin keratinocytes that contribute to HBD-2 gene expression upon stimulation with AV119. Our data provide information on signalling pathways in which the activation of protein tyrosine kinases (PTKs) and protein kinase C (PKC) takes place and leads to AP-1 and HBD-2 gene activation.
Paoletti
Iole
I
Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Via Costantinopoli 16, Naples, Italy.
Buommino
Elisabetta
E
Tudisco
Laura
L
Baudouin
Caroline
C
Msika
Philippe
P
Tufano
Maria Antonietta
MA
Baroni
Adone
A
Donnarumma
Giovanna
G
D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002241:Carbohydrates / Q000494:pharmacology*; D002478:Cells, Cultured; D004789:Enzyme Activation; D005638:Fruit; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D027421:Persea; D010936:Plant Extracts / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000073893:Sugars; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
C549768:AV119; D000890:Anti-Infective Agents; D002241:Carbohydrates; C106641:DEFB4A protein, human; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D000073893:Sugars; D018808:Transcription Factor AP-1; D023083:beta-Defensins; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C