Deletion of Cdk5 in Macrophages Ameliorates Anti-Inflammatory Response during Endotoxemia through Induction of C-Maf and Il-10.
Int J Mol Sci
; 22(17)2021 Sep 06.
Article
en En
| MEDLINE
| ID: mdl-34502552
ABSTRACT
Immune response control is critical as excessive cytokine production can be detrimental and damage the host. Interleukin-10 (Il-10), an anti-inflammatory cytokine produced primarily by macrophages, is a key regulator that counteracts and controls excessive inflammatory response. Il-10 expression is regulated through the transcription factor c-Maf. Another regulator of Il-10 production is p35, an activator of the cyclin-dependent kinase 5 (Cdk5), which decreases Il-10 production in macrophages, thus increasing inflammation. However, Cdk5 regulation of c-Maf and the involvement of Il-10 production in macrophages has not yet been investigated. We used in vitro primary bone marrow-derived macrophages (BMDMs) lacking Cdk5, stimulated them with lipopolysaccharid (LPS) and observed increased levels of c-Maf and Il-10. In an in vivo mouse model of LPS-induced endotoxemia, mice lacking Cdk5 in macrophages showed increased levels of c-Maf and elevated levels of Il-10 in lungs as well as in plasma, resulting in ameliorated survival. Taken together, we identified Cdk5 as a potential novel regulator of Il-10 production through c-Maf in macrophages under inflammatory conditions. Our results suggest that inhibition of Cdk5 enhances the c-Maf-Il-10 axis and thus potentiates improvement of anti-inflammatory therapy.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Interleucina-10
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Endotoxemia
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Quinasa 5 Dependiente de la Ciclina
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Proteínas Proto-Oncogénicas c-maf
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Inflamación
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Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2021
Tipo del documento:
Article
País de afiliación:
Alemania