Epigallocatechin-3-gallate attenuates the AIM2-induced secretion of IL-1β in human epidermal keratinocytes.
The pro-inflammatory cytokine interleukin-1β (IL-1β) plays a central role in the pathogenesis of psoriasis. Keratinocytes are a major source of IL-1β and express absent in melanoma 2 (AIM2). AIM2 recognizes a double-stranded DNA and initiates the IL-1β-processing of inflammasome. The AIM2 inflammasome is a cytosolic multiprotein complex composed of AIM2, an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1. Epigallocatechin-3-Gallate (EGCG), a major polyphenolic component of green tea, has anti-inflammatory properties. In the current study, we investigated the issue of whether or how EGCG suppresses AIM2 inflammasome in human epidermal keratinocytes, neonatal (HEKn). Treatment with EGCG, before or after IFN-γ priming, attenuated poly(dA:dT)-induced IL-1β secretion in HEKn cells. Pre-treatment with EGCG reduced the level of IFN-γ-induced priming signal via the down-regulation of pro-IL-1β and pro-capspase-1 in HEKn cells. Furthermore, treatment with EGCG attenuated poly(dA:dT)-induced ASC oligomerization and caspase-1 activation in IFN-γ-primed HEKn cells. These results suggest that EGCG attenuates AIM2-induced IL-1β secretion by suppressing both IFN-γ-mediated priming and poly(dA:dT)-induced ASC oligomerization of inflammasomes in human epidermal keratinocytes.
Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea.
Mihee
M
Yun
Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea.
Gimoon
G
Seo
Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea.
Ji-Young
JY
Lee
Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea.
Gue Tae
GT
Chae
Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea. Electronic address: sblee@catholic.ac.kr.
Seong-Beom
SB
Lee
D020170:Caspase 1 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000502:physiology; D053583:Interleukin-1beta / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects*
C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D007371:Interferon-gamma; D002392:Catechin; C045651:epigallocatechin gallate; D020170:Caspase 1
Absent in melanoma 2; Epigallocatechin-3-gallate; Inflammasome; Interleukin-1β; Keratinocyte