Role of nucleotide binding oligomerization domain-like receptor protein 3 inflammasome in stress-induced gastric injury.
J Gastroenterol Hepatol
; 36(3): 740-750, 2021 Mar.
Article
in En
| MEDLINE
| ID: mdl-32918847
ABSTRACT
BACKGROUND AND AIM:
The inflammasomes promote pro-caspase-1 cleavage, leading to processing of pro-interleukin (IL)-1ß into its mature form. We investigated the role of the IL-1ß and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in gastric injury in mice receiving water-immersion restraint stress (WIRS), focusing on the cyclooxygenase (COX)-2/prostaglandin (PG) E2 axis.METHODS:
To induce gastric injury, the mice were placed in a restraint cage and immersed in the water bath to the level of the xiphoid process. Protein levels of mature caspase-1 and IL-1ß were assessed by western blotting.RESULTS:
Water-immersion restraint stress induced gastric injury with increase in IL-1ß expression by activation of NLRP3 inflammasome. Exogenous IL-1ß attenuated the injury, whereas anti-IL-1ß neutralizing antibody and IL-1ß receptor antibody aggravated it. NLRP3-/- and caspase-1-/- mice enhanced the injury with reducing of mature IL-1ß, and this aggravation was reduced by exogenous IL-1ß supplementation. Toll-like receptor 4-/- mice were hyporesponsive to WIRS in terms of mature IL-1ß production. Rabeprazole attenuated the injury with preventing inflammasome activation. WIRS injured the stomach with promotion of COX-2 mRNA and PGE2 production, and exogenous IL-1ß enhanced these molecules, while IL-1ß immunoneutralization exerted opposite effect. PGE2 supplementation abolished the hypersensitivity in NLRP3-/- and caspase-1-/- mice through negative regulation of inflammatory cytokines.CONCLUSION:
These results suggest that NLRP3 inflammasome-derived IL-1ß plays a protective role in stress-induced gastric injury via activation of the COX-2/PGE2 axis. Toll-like receptor 4 signaling and gastric acid may be involved in NLRP3 inflammasome activation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stomach Diseases
/
Stress, Psychological
/
Interleukin-1beta
/
Inflammasomes
/
NLR Family, Pyrin Domain-Containing 3 Protein
Limits:
Animals
Language:
En
Journal:
J Gastroenterol Hepatol
Journal subject:
GASTROENTEROLOGIA
Year:
2021
Type:
Article
Affiliation country:
Japan