Curcumin inhibits poly(dA:dT)-induced IL-18 secretion by inhibiting the ASC oligomerization in human keratinocytes

Abstract

Interleukin (IL)-18, a member of the IL-1 family, has been implicated in the development of a variety of inflammatory skin diseases. The binding of double-stranded (ds) DNA to absent in melanoma (AIM) 2 induces the oligomerization of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and the recruitment of pro-caspase-1, which leads to the activation of caspase-1, subsequently resulting in the secretion of IL-1β and IL-18. Curcumin is a naturally occurring polyphenolic compound in Curcuma longa and is also well known to have anti-oxidant and anti-inflammatory properties. In the current study, we focused on the inhibitory effect of curcumin on ASC oligo-merization in human keratinocytes. The IL-18 level was measured by using an ELISA kit. The protein levels of AIM2 inflammasome components, such as AIM2, ASC, and pro-caspase-1, were determined by using a western blot. The level of ASC oligomerization was also determined by using a western blot. Our results show pre-treatment with curcumin attenuated poly (dA:dT)-induced secretion of IL-18 in IFN-γ-primed human keratinocytes. Pre-treatment with 10 µM curcumin was also found to inhibit ASC oligomerization in IFN-γ-primed cells. These collective results show that curcumin inhibits the poly (dA:dT)-induced secretion of IL-18 via the suppression of ASC oligomerization in IFN-γ-primed human keratinocytes.