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.