Cathepsin B aggravates acute pancreatitis by activating the NLRP3 inflammasome and promoting the caspase-1-induced pyroptosis.
Int Immunopharmacol
; 94: 107496, 2021 May.
Article
em En
| MEDLINE
| ID: mdl-33639565
ABSTRACT
OBJECTIVES:
Cathepsin B (CTSB), nod-like receptor family pyrin domain-containing 3 (NLRP3), and caspase-1 play an important role in the development of Acute Pancreatitis (AP). Besides, the relationship between the proteins remains poorly understood. In addition, whereas previous studies have found caspase-1 activation in AP, pyroptosis, a caspase-1 induced cell death mode, has never been proposed and proved in AP.METHODS:
We induced AP in mice by intraperitoneal injection of cerulein. Mice in the inhibitor group of CTSB were pretreated with injection of CA-074me, while mice in the inhibitor group of caspase-1 were of Ac-YVAD-CHO, 1 h earlier. We evaluated the inflammation of the pancreas and the detected expression of activated CTSB, NLRP3, ASC, caspase-1p20, IL-1ß and IL-18. TUNEL staining was used to detect acinar cell death.RESULTS:
The inflammation of the pancreas in the two inhibitor groups was significantly reduced compared with that in the AP group. We observed that CA-074me not only inhibits CTSB, but also suppresses the expression and activity of NLRP3, ASC and caspase-1. We found that CA-074me further inhibits the downstream event of caspase-1, including pro-inflammatory cytokine secretion and pyroptosis. Whereas Ac-YVAD-CHO inhibited caspase-1 and decreased pro-inflammatory cytokine secretion and pyroptosis, it did not down-regulate the expression and activity ofCTSB, NLRP3 and ASC.CONCLUSION:
The results indicate that CTSB may aggravate AP by activating the NLRP3 inflammasome and promoting Caspase-1-induced pyroptosis. These provide clues about the pathophysiological mechanisms of AP, shedding light on new ideas and potential targets for the prevention and treatment of AP.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Pancreatite
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Catepsina B
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article