Potential synergy between SNP and CpG-A or IL-1β in regulating transcriptional activity of IL-20 promoter

Abstract

Psoriasis is a multifactorial cutaneous disorder that in many aspects is influenced by both genetic and environmental elements. IL-20, a member of IL-10 family, is found to be involved in the development of psoriasis. In our previous study, a single-nucleotide polymorphism (SNP) of IL-20-1723C→G (rs1713239) was found to be associated with psoriasis progression, especially in those induced by upper respiratory tract infection. To further explore the underlying mechanism, we investigated the function of this specific variant and its cooperative effect with bacterial-like DNA or IL-1β on regulating IL-20 expression. We found that in HaCat cells, both IL-1β and CpG-A triggered a stronger IL-20 promoter activity with the risk-associated G allele in comparison with the nonrisk C allele of rs1713239. Furthermore, on stimulation with IL-1β or CpG-A, an increased level of IL-20 expression was also observed in psoriatic lesions of patients carrying the risk-associated G allele. This study demonstrates that rs1713239 and infection may have potential synergetic effect on modulating the transcriptional activity of IL-20. © 2014 The Society for Investigative Dermatology.