IL-33 is regulated by TNF-α in normal and psoriatic skin

Interleukin-33 (IL-33) is the most recently discovered IL-1 family member. Considered an endogenous "alarmin" released by necrotic cells in response to tissue injury or damage, IL-33 is constitutively expressed in tissues exposed to the environment, where endothelial and epithelial cells constitute its major sources. Several findings reported that pro-inflammatory stimuli, such as IFN-gamma and TNF-alpha, as well as IL-17, can induce IL-33 expression in normal human epidermal keratinocytes. In the present study, we deeply investigated the relation between IL-33 and TNF-alpha, by employing the whole skin as study model. TNF-alpha dose- and time-dependently induced IL-33 gene expression in ex vivo healthy skin organ culture. Similarly, TNF-alpha significantly increased IL-33 mRNA expression in normal human epidermal sheets. Moreover, IL-33 was enhanced in psoriatic skin and anti-TNF-alpha therapy was able to significantly reduce it. The biology of IL-33 is gaining in complexity, and this molecule is now known to have additional roles beyond its original description. In particular, we can assess that IL-33 is regulated by TNF-alpha in normal and psoriatic skin.