IL-12, IL-23, and IL-27 enhance human beta-defensin-2 production in human keratinocytes.
IL-12, IL-23, and IL-27, which are produced by APC, modulate innate and adaptive immunities. Human beta-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-1beta-induced hBD-2 secretion and mRNA expression in keratinocytes. The stimulatory effects of IL-12, IL-23, and IL-27 were suppressed by antisense oligonucleotides against NF-kappaB p50 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-1beta-induced transcriptional activities of NF-kappaB, while IL-12 and IL-27 enhanced STAT3 and STAT1 activities, respectively. Further, IL-12, IL-23, and IL-27 promoted basal and IL-1beta-induced phosphorylation of IkappaBalpha. 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 phosphorylated JAK1. These results suggest that IL-12, IL-23, and IL-27 may enhance IL-1beta-induced hBD-2 production in keratinocytes by activating NF-kappaB. STAT3 and STAT1 are involved in the effects 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.
Kanda
Naoko
N
Department of Dermatology, Teikyo University, School of Medicine, Tokyo, Japan. nmk@med.teikyo-u.ac.jp
Watanabe
Shinichi
S
D050822:Cytokine Receptor gp130 / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology*; D053711:Interleukin-12 Receptor beta 1 Subunit / Q000235:genetics; D053712:Interleukin-12 Receptor beta 2 Subunit / Q000235:genetics; D053583:Interleukin-1beta / Q000494:pharmacology; D053759:Interleukin-23 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology*; D053613:Janus Kinase 1 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D053634:TYK2 Kinase / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism*
C106641:DEFB4A protein, human; D020672:I-kappa B Proteins; C515500:IL23R protein, human; C112441:IL27RA protein, human; C494199:IL6ST protein, human; D053711:Interleukin-12 Receptor beta 1 Subunit; D053712:Interleukin-12 Receptor beta 2 Subunit; D053583:Interleukin-1beta; D053759:Interleukin-23; D007378:Interleukins; C464565:MYDGF protein, human; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D034741:RNA, Small Interfering; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D023083:beta-Defensins; D050822:Cytokine Receptor gp130; D000072000:NF-KappaB Inhibitor alpha; D018664:Interleukin-12; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053634:TYK2 Kinase; C070139:TYK2 protein, human