Interaction of Neutrophils with Macrophages Promotes IL-1ß Maturation and Contributes to Hepatic Ischemia-Reperfusion Injury.
J Immunol
; 199(9): 3306-3315, 2017 11 01.
Article
em En
| MEDLINE
| ID: mdl-28972095
ABSTRACT
Accumulating evidence suggests that IL-1ß plays a pivotal role in the pathophysiology of hepatic ischemia-reperfusion (I/R) injury; however, the mechanism by which I/R triggers IL-1ß production in the liver remains unclear. Recent data have shown that neutrophils contribute to hepatic I/R injury independently of the inflammasomes regulating IL-1ß maturation. Thus, we investigated the role of neutrophils in IL-1ß maturation and tissue injury in a murine model of hepatic I/R. IL-1ß was released from the I/R liver and its deficiency reduced reactive oxygen species generation, apoptosis, and inflammatory responses, such as inflammatory cell infiltration and cytokine expression, thereby resulting in reduced tissue injury. Depletion of either macrophages or neutrophils also attenuated IL-1ß release and hepatic I/R injury. In vitro experiments revealed that neutrophil-derived proteinases process pro-IL-1ß derived from macrophages into its mature form independently of caspase-1. Furthermore, pharmacological inhibition of serine proteases attenuated IL-1ß release and hepatic I/R injury in vivo. Taken together, the interaction between neutrophils and macrophages promotes IL-1ß maturation and causes IL-1ß-driven inflammation in the I/R liver. Both neutrophils and macrophages are indispensable in this process. These findings suggest that neutrophil-macrophage interaction is a therapeutic target for hepatic I/R injury and may also provide new insights into the inflammasome-independent mechanism of IL-1ß maturation in the liver.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
/
Comunicação Celular
/
Interleucina-1beta
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Fígado
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Hepatopatias
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Macrófagos
/
Neutrófilos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2017
Tipo de documento:
Article