Back to Search
Start Over
SOCS3 protects against neonatal necrotizing enterocolitis via suppressing NLRP3 and AIM2 inflammasome activation and p65 nuclear translocation
- Source :
- Molecular immunology. 122
- Publication Year :
- 2020
-
Abstract
- Background Necrotizing enterocolitis (NEC) is an acquired disorder of mucosal damage characterized by the diffuse or local necrosis of the intestine. The suppressor of cytokine signaling 3 (SOCS3) has been demonstrated to possess anti-inflammatory action in gastritis, ulcerative colitis and other inflammatory diseases. The present study aims to explore the effects of SOCS3 on LPS-induced colonic cell model of NEC, and investigate the underlying mechanisms. Methods Expression of SOCS3 in tissue samples of NEC and LPS-induced enterocytes were evaluated by real-time quantitative PCR (RT-qPCR). Western blotting and enzyme-linked immunosorbent assay (ELISA) were applied to examine the effect of SOCS3 on inflammatory molecules. Co-immunoprecipitation assay were devoted to explore the relation between SOCS3 and TLR4. Results We proved that SOCS3 was expressed at a low level in tissue samples of NEC and LPS-induced enterocytes, and LPS inhibited SOCS3 expression via JAK2/STAT3 pathway. Overexpression of SOCS3 weaken the LPS-induced inflammatory response in FHC and CACO2 cells. Moreover, SOCS3 downregulates proinflammatory cytokines by targeting TLR4, thus mediating the p65 nuclear translocation, and the activation of NLR family pyrin domain containing 3/absent in melanoma-2 (NLRP3/AIM2) inflammasome, ultimately reveals its anti-inflammatory effects. Conclusions Taken together, our data revealed that LPS inhibited SOCS3 expression via JAK2/STAT3 pathway, and SOCS3 protects enterocytes against NEC through mediating p65 nuclear translocation and NLRP3/AIM2 inflammasome activation in a TLR4 dependent manner.
- Subjects :
- 0301 basic medicine
Necrosis
biology
Chemistry
digestive, oral, and skin physiology
Immunology
Inflammasome
Pyrin domain
Proinflammatory cytokine
03 medical and health sciences
AIM2
030104 developmental biology
0302 clinical medicine
Cancer research
medicine
biology.protein
TLR4
SOCS3
medicine.symptom
STAT3
Molecular Biology
030215 immunology
medicine.drug
Subjects
Details
- ISSN :
- 18729142
- Volume :
- 122
- Database :
- OpenAIRE
- Journal :
- Molecular immunology
- Accession number :
- edsair.doi.dedup.....28f367fb024288c4fd01bcc1530a1c75