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 and adaptive immunities. Human b-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-1b-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-jB 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-1b-induced transcriptional activities of NF-jB, while IL-12 and IL-27 enhanced STAT3 and STAT1 activities, respectively. Further, IL-12, IL-23, and IL-27 promoted basal and IL-1b-induced phosphorylation of IjBa. 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-1b-induced hBD-2 production in keratinocytes by activating NF-jB. 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.

A Novel Role for Interleukin-27 (IL-27) as Mediator of Intestinal Epithelial Barrier Protection Mediated via Differential Signal Transducer and Activator of Transcription (STAT) Protein Signaling and Induction of Antibacterial and Anti-inflammatory Proteins

“…IL-27 also activates the transcription factors STAT1, STAT3, and STAT6. STAT1 and STAT3 activation by IL-27 has been shown in other studies in T cells, monocytes, and keratinocytes (22,23). However, this is the first study reporting phosphorylation of STAT6 by IL-27.…”

New Interleukins in Psoriasis and Psoriatic Arthritis Patients: The Possible Roles of Interleukin-33 to Interleukin-38 in Disease Activities and Bone Erosions

“…IL-23 secreted by skin dendritic cells induces the production of IL-17 and IL-22 by Th17 cells. These mediators will act on keratinocytes leading to their activation and hyperproliferation, which then recruit and activate immune cells in the inflamed skin [20] . Furthermore, Zaba et al [21] showed that anti-TNF-α agents are able to modulate IL-23p19 and IL-12p40 mRNA levels as well as the inflammatory infiltration in the psoriatic skin lesions.…”

Expression of hBD-2 induced by 23-valent pneumococcal polysaccharide vaccine, Haemophilus influenzae type b vaccine and split influenza virus vaccine

“…Besides microorganisms, LTB4, L12, L23, L27 and certain other immune factors also induce the expression of hBD-2 (24,28). However, using these microorganisms to study the regulation and function in vivo and in vitro often leads to the threat of a biological hazard.…”