TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-κBs pathway

Abstract

Introduction: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. Methods: The colitis model was established on mice through DSS induction. For the TRIM52 knock-down, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. Results: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. Conclusion: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a tar-get of therapeutic treatment.

Lactobacillus rhamnosus GG triggers intestinal epithelium injury in zebrafish revealing host dependent beneficial effects

“…In line with these studies, the importance of zTLR4ba to SpaC‐induced pyroptosis was also validated by the knockdown of TLR4ba in zebrafish larvae. In line with our findings, the inhibition or activation of the TLR4 signal pathway can inhibit or activate intestinal pyroptosis in mammals [ 69 , 70 , 71 , 72 ]. Therefore, the causal functional relationship between TLR4 signaling and cell pyroptosis is conserved among zebrafish and mammals.…”

“…Seven membrane receptors were screened by using pull‐down assay conjugating LC−MS/MS technique, including TLR4ba. Among these receptors, existing reports suggest that only TLR4 is reported to control pyroptosis in mammals [ 69 , 70 , 71 , 72 ]. In line with these studies, the importance of zTLR4ba to SpaC‐induced pyroptosis was also validated by the knockdown of TLR4ba in zebrafish larvae.…”

TRIM52 is a primate-specific player in the DNA repair process under tight proteolytic control by a triad of giant E3 ligases

“…TRIM52 has been under positive selection pressure in humans and old-world primates. In contrast to other TRIM proteins with similar evolutionary patterns-like TRIM5α-no evidence has been found for direct anti-retroviral activity of TRIM52 6 , although some studies have reported a role in defenses against other viruses and inflammatory signaling 10,[54][55][56] . In agreement with cell-intrinsic selection pressure, rather than pressure exclusively from exogenous pathogens, we found that TRIM52 ablation decreased cellular fitness in a p53-dependent manner, in the absence of external stimuli 8,9 .…”