TRIM31 inhibits NLRP3 inflammasome and pyroptosis of retinal pigment epithelial cells through ubiquitination of NLRP3

Abstract

NOD-like receptor protein 3 (NLRP3) is associated with age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells serve as the immune defense of macula, and their dysfunction causes clinically relevant changes in AMD. In the present study, oxidized low-density lipoprotein (ox-LDL) activated the NLRP3 inflammasome in human RPE cell line ARPE-19. Our data showed that the expression of NLRP3, interleukin-1β (IL-1β), and caspase-1 and the release of IL-1β in ARPE-19 cells were substantially increased by ox-LDL, whereas the addition of NLRP3 inhibitor INF39 dose-dependently reversed the effect of ox-LDL. Overexpression of tripartite motif-containing protein 31 (TRIM31) also suppressed the effect of ox-LDL in ARPE-19 cells. TRIM31 knockdown had similar effects with ox-LDL but INF39 could block the effect of TRIM31 knockdown. Moreover, TRIM31 could interact with NLRP3 in ARPE-19 cells. Overexpression of TRIM31 increased NLRP3 ubiquitination. In conclusion, the results propose that TRIM31 could enhance NLRP3 ubiquitination, therefore inhibiting NLRP3 inflammasome and pyroptosis in human RPE cells.

Mulberrin confers protection against hepatic fibrosis by Trim31/Nrf2 signaling

“…TRIM31/NLRP3 signaling is involved in the mediation of inflammation under various stimuli [ 13 , 14 ], and was previously reported to regulate NF-κB pathway to subsequently control various cellular events, particularly inflammatory response [ 9 ]. Here, we notably found that CCl 4 challenge significantly reduced the expression of TRIM31 in liver samples, evidenced by the weakened fluorescent intensity; however, such effect was greatly abolished by Mul treatments ( Fig.…”

“…Approaches to restrain inflammation, ROS production and collagen deposition are pivotal and promising for the treatment of liver fibrosis [ 10 , 20 , 22 ]. Mulberrin (Mul), as a key component of Chinese medicine Romulus Mori , has anti-inflammatory and antioxidant properties to meliorate tissue injury [ 13 , 14 ].…”

“…Recently, TRIM31 was shown to attenuate NLRP3 inflammasome activation, subsequently accelerating IL-1β releases and alum-induced peritonitis in vivo [ 13 ]. More recently, TRIM31 over-expression was reported to reduce the effects of oxidized low-density lipoprotein (ox-LDL) on NLRP3 expression, pyroptosis, and inflammatory cytokine levels in vitro [ 14 ]. Under stimuli conditions, NLRP3 assembles into a large cytoplasmic complex through recruiting apoptosis associated speck-like protein (ASC) and Caspase-1, thereafter, causing the cleavage of pro-IL-1β, which enables its maturation and releases from cells depending on NF-κB activation [ 15 ].…”

Do inflammasome impact COVID-19 severity?

“…Moreover, TRIM31 appears to be an inflammasome suppressor through feedback positive because induces Lys48-linked ubiquitination. Besides, the Ser295 in NLRP3 is an important site to phosphorylation by protein kinase A (PKA) and subsequent inhibition of inflammasome activation [29,30].…”

Emerging Roles of MHC Class I Region-Encoded E3 Ubiquitin Ligases in Innate Immunity

“…The study also showed that Trim31 deficiency aggravates alum-induced peritonitis and attenuates the severity of DSSinduced colitis (45). Furthermore, TRIM31 reduces the risk of other NLRP3 inflammasome-associated diseases such as apical periodontitis (AP, an acute suppurative inflammation caused by endodontic microbial infections) and age-related macular degeneration (AMD, a major cause of blindness in the elderly in developed countries, induced by dysfunction of retinal pigment epithelial cells, which constitute the immune defense barrier of the macula) (46,47). In addition, TRIM31 is involved in the development of sepsis and colorectal cancer through regulating the NF-kB signaling pathway (48,49).…”