Neutrophils-derived Spink7 as one safeguard against experimental murine colitis.
Biochim Biophys Acta Mol Basis Dis
; 1867(6): 166125, 2021 06 01.
Article
em En
| MEDLINE
| ID: mdl-33722746
ABSTRACT
The uncontrolled abnormal intestinal immune responses play important role in eliciting inflammatory bowel disease (IBD), yet the molecular events regulating intestinal inflammation during IBD remain poorly understood. Here, we describe an endogenous, homeostatic pattern that controls inflammatory responses in experimental murine colitis. We show that Spink7 (serine peptidase inhibitor, kazal type 7), the ortholog of human SPINK7, is significantly upregulated in dextran sodium sulfate (DSS)-induced murine colitis model. Spink7-deficient mice showed highly susceptible to experimental colitis characterized by enhanced weight loss, shorter colon length, higher disease activity index and increased colonic tissue destruction. Bone marrow reconstitution experiments demonstrated that expression of Spink7 in the immune compartment makes main contribution to its protective role in colitis. What's more, neutrophils are the primary sources of Spink7 in experimental murine colitis. Loss of Spink7 leads to augmented productions of multiple chemokines and cytokines in colitis. In summary, this study identifies neutrophils-derived endogenous Spink7-mediated control of chemokines/cytokines production as a molecular mechanism contributing to inflammation resolution during colitis.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Serina Proteinase
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Citocinas
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Sulfato de Dextrana
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Colite
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Quimiocinas
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Inibidores de Serinopeptidase do Tipo Kazal
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Neutrófilos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article