Increased Interleukin-36β Expression Promotes Angiogenesis in Japanese Atopic Dermatitis.

While atopic dermatitis (AD) is considered as a T helper 2 (Th2)-centered disease, an increase in other types of inflammatory cytokines is also noted in AD and they may also contribute to the development of the disease. Recently, the efficacy of an anti-IL-36 receptor antibody in AD was demonstrated in a clinical trial. Although there have been several reports on IL-36α and IL-36γ expression and function in AD, IL-36β has been barely studied. In this report, we examined IL-36β expression and function using clinical samples of AD and the epidermal keratinocyte cell line, HaCaT cells. We demonstrated that IL-36β expression in epidermal keratinocytes was increased in AD lesional skin compared to healthy skin. IL-36β promoted vascular endothelial growth factor A production in HaCaT keratinocytes through phosphorylation of extracellular signal-regulated kinases 1 and 2. In addition, IL-36β up-regulated placental growth factor mRNA expression in HaCaT keratinocytes. IL-36β expression levels in epidermal keratinocytes were correlated with the number of dermal vessels in AD skin. These results suggest that IL-36β may play an important role for angiogenesis in lesional skin of AD and that IL-36β can be a therapeutic target in AD.