IL-12, IL-23, and IL-27 enhance human β-defensin-2 production in human keratinocytes

Abstract

IL-12, IL-23, and IL-27, which are produced by APC, modulate innate an adaptive immunities. Human β-defensin-2 (hBD,-2) produced by epidermal keratinocytes promotes cutaneous antimicrobial defense" and inflammation. We examined the in vitro effects of IL-12, IL-23, and IL-27 on hBD-2 production in human keratinocytes. IL-12, IL-23, and IL-27 enhanced IL-1β-induced hBD-2 $ecretion and mRNA expression in keratinocytes. The stimulatory effects of IL-22, IL-23,and IL-27 were suppressed by antisense oligonucleotides against NF-κB p5O and p65. In addition, the effects of IL-12 and IL-27 were suppressed by antisense STAT3 and STAT1, respectively. All the three IL enhanced the basal and IL-1β-induced transcriptional activities of NF-κB, while IL-12 and IL-27 enhanced STAT3 and STAT1 activities, respectively. Further, IL-12, IL-23, and IL-27 promoted basal and IL-1β-induced phosphorylation of IκBα. IL-12 and IL-23 tyrosine phosphorylated STAT3 and STAT1, respectively; IL-12, IL-23, and IL-27 tyrosine phosphorylated JAK2 and tyrosine kinase-2; and IL-27 tyrosine phoqphorylated JAK1. These results suggest that IL-12, IL-23, and IL-27 may enhance IL-1β-induced hBD-2 production in keratinocytes by activating NF-κB. STAT3 and STAT1 are involved in the eflects of IL-12 and IL-27, respectively. Thus, IL-12, IL-23, and IL-27 may promote cutaneous antimicrobial defense and inflammation via hBD-2. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.