E3 ubiquitin ligase alleviates DSS-induced colitis via regulating NLRP3 inflammasome activation
10.3969/j.issn.1006-2483.2022.03.002
- VernacularTitle:E3泛素连接酶TRIM65通过调控NLRP3炎症小体的活化改善DSS诱导的结肠炎
- Author:
Tiantian TANG
1
,
2
,
3
;
Wei HAN
1
,
2
,
3
;
Ping LI
1
,
2
,
3
;
Mengyi YANG
1
,
2
,
3
;
Xiuqin FAN
1
,
2
,
3
;
Rui WANG
1
,
2
,
3
;
Kemin QI
1
,
2
,
3
Author Information
1. Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children'
2. s Hospital, Capital Medical University, National Center for Children'
3. s Health, Beijing, China , 100045
- Publication Type:Journal Article
- Keywords:
Colitis;
TRIM65;
NLRP3 inflammasome;
Dextran sulfate sodium
- From:
Journal of Public Health and Preventive Medicine
2022;33(3):6-11
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of TRIM65 on DSS induced colitis and the underlying molecular mechanisms. Methods Trim65+/+ and Trim65-/- mice were administered with 3% (w/v) DSS in their drinking water for 5 consecutive days and then were switched to sterile water for 2 days. DSS treated mice were monitored daily for the clinical symptoms (bodyweight, stool consistency and rectal bleeding score). Mice were sacrificed on day 7 to measure colon length. Colon homogenates were collected to measure MPO activity and detect cleaved caspase-1 and mature IL-1β by Enzyme linked immunosorbent assay (ELISA) and Western blot. Trim65-/- mice were intraperitoneally injected with NLRP3 inflammasome inhibitor MCC950, and were given the above treatment to determine the effect of MCC950 on colitis in Trim65-/- mice. Results The results showed that deletion of Trim65 significantly enhanced weight loss and colon shortening in DSS mice, increased disease activity index and histopathological score, induced the activity of MPO, and promoted the F4/80+ immune cell infiltration, the activation of caspase-1 and the secretion of mature IL-1 in the colon of DSS mice. The NLRP3 inflammasome inhibitor MCC950 alleviated DSS induced colitis symptoms and inflammation levels in trim65 deficient mice. Conclusion TRIM65 plays an anti-inflammatory role in DSS induced colitis mice by inhibiting the activation of NLRP3 inflammasome.
