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

Molecular & Cellular Toxicology 2019년 15권 4호 p.399 ~ 406
 ( Lee Yu-Jin ) - Catholic University College of Medicine Department of Pathology

 ( Kang Jung-Hoon ) - Catholic University College of Medicine Department of Pathology
 ( Yun Mi-Hee ) - Catholic University College of Medicine Department of Pathology
 ( Lee Seong-Beom ) - Catholic University College of Medicine Department of Pathology

Abstract


Backgrounds: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

키워드

Curcumin; AIM 2; Inflammasome; Keratinocytes; ASC
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