title: The caspase-1 inhibitor AC-YVAD-CMK attenuates acute gastric injury in mice: involvement of silencing NLRP3 inflammasome activities.
abstract: This study evaluated the protective effects of inhibiting caspase-1 activity or gastric acid secretion on acute gastric injury in mice. AC-YVAD-CMK, omeprazole, or vehicle were administered to mice before cold-restraint stress- or ethanol-induced gastric injury. Survival rates and histological evidence of gastric injury of mice pretreated with AC-YVAD-CMK or omeprazole, and exposed to cold-restraint stress, improved significantly relative to the vehicle group. The increased levels of tumour necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-18 following cold-stress injury were decreased by AC-YVAD-CMK, but not omeprazole, pretreatment. The increased expression of CD68 in gastric tissues was inhibited significantly by AC-YVAD-CMK pretreatment. Inhibiting caspase-1 activity in the NLRP3 inflammasome decreased gastric cell apoptosis, and the expression of Bax and cleaved caspase-3. AC-YVAD-CMK pretreatment significantly inhibited cold-restraint stress-induced increases in the expression of phosphorylated IκB-alpha and P38. General anatomy and histological results showed the protective effect of AC-YVAD-CMK on ethanol-induced acute gastric injury. Overall, our results showed that the caspase-1 inhibitor AC-YVAD-CMK protected against acute gastric injury in mice by affecting the NLRP3 inflammasome and attenuating inflammatory processes and apoptosis. This was similar to the mechanism associated with NF-κB and P38 mitogen-activated protein kinase signalling pathways.
authors.affiliation: Department of Burn Surgery, the Second Military Medical University Affiliated Changhai Hospital, Shanghai 200433, China.|Number 73901 Troop of PLA, Shanghai 200439.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Burn Surgery, the Second Military Medical University Affiliated Changhai Hospital, Shanghai 200433, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Burn Surgery, the Second Military Medical University Affiliated Changhai Hospital, Shanghai 200433, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Burn Surgery, the Second Military Medical University Affiliated Changhai Hospital, Shanghai 200433, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Luo
authors.affiliation: Department of Burn Surgery, the Second Military Medical University Affiliated Changhai Hospital, Shanghai 200433, China.
authors.forename: Xing-Tong
authors.initials: XT
authors.lastname: Wang
authors.affiliation: Department of Burn Surgery, the Second Military Medical University Affiliated Changhai Hospital, Shanghai 200433, China.
authors.forename: Zhao-Fan
authors.initials: ZF
authors.lastname: Xia
mesh_terms: D000208:Acute Disease; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020170:Caspase 1 / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000633:toxicity; D003080:Cold Temperature / Q000009:adverse effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D058847:Inflammasomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism*; D012149:Restraint, Physical / Q000009:adverse effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013272:Stomach Diseases / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D002492:Central Nervous System Depressants; D015853:Cysteine Proteinase Inhibitors; D016207:Cytokines; D058847:Inflammasomes; C098738:N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D000431:Ethanol; D048051:p38 Mitogen-Activated Protein Kinases; D020170:Caspase 1