Identification of deubiquitinases involved in the regulation of NLRP3 inflammasome activity through DUB siRNA library screening

다국어 초록 (Multilingual Abstract)

Inflammasome, the cytosolic complex consists of ligand recognizing receptor, ASC and caspase-1, performs as a key mediator in inflammatory responses by maturating inflammatory cytokines, IL-1β and IL-18. Since the uncontrolled activity of inflammasome could induce critical inflammatory diseases, the activation of inflammasome should be tightly regulated. Although the involvement of deubiquitination is steadily reported in the NLRP3 inflammasome signaling, it is still unknown that which DUB(s) is(are) performing this regulation. Using deubiquitinase-targeting siRNA library, this study identified positive and negative regulators for NLRP3 inflammasome activation. Repetitive examinations revealed that A20 (also known as TNFAIP3) knockdown significantly increased the secretion of IL-1β whereas USP50 knockdown showed the opposite. Molecular approaches revealed that A20 is carrying out regulatory role for NLRP3 inflammasome and probably AIM2 inflammasome signaling. On the other hand, USP50 knockdown showed little regulatory effect on AIM2 inflammasome activation. These observations suggest two DUBs, A20 and USP50, as important regulators for NLRP3 inflammasome signaling and give us insight for the regulating mechanisms involved in NLRR3 inflammasomes.

목차 (Table of Contents)

• I.Abstract 1
• II.Introduction 2
• III.Material and methods 5
• IV.Results 9
• V.List of figures 15
• VI.Discussion 24
• VII.Reference 26
• VIII.국문요약 32