Decreased Protein Kinase C-ß Type II Associated with the Prominent Endotoxin Exhaustion in the Macrophage of FcGRIIb-/- Lupus Prone Mice is Revealed by Phosphoproteomic Analysis.
Int J Mol Sci
; 20(6)2019 Mar 18.
Article
em En
| MEDLINE
| ID: mdl-30889825
ABSTRACT
Dysfunction of FcGRIIb, the only inhibitory receptor of the FcGR family, is commonly found in the Asian population and is possibly responsible for the extreme endotoxin exhaustion in lupus. Here, the mechanisms of prominent endotoxin (LPS) tolerance in FcGRIIb-/- mice were explored on bone marrow-derived macrophages using phosphoproteomic analysis. As such, LPS tolerance decreased several phosphoproteins in the FcGRIIb-/- macrophage, including protein kinase C-ß type II (PRKCB), which was associated with phagocytosis function. Overexpression of PRKCB attenuated LPS tolerance in RAW264.7 cells, supporting the role of this gene in LPS tolerance. In parallel, LPS tolerance in macrophages and in mice was attenuated by phorbol 12-myristate 13-acetate (PMA) administration. This treatment induced several protein kinase C families, including PRKCB. However, PMA attenuated the severity of mice with cecal ligation and puncture on LPS tolerance preconditioning in FcGRIIb-/- but not in wild-type cells. The significant reduction of PRKCB in the FcGRIIb-/- macrophage over wild-type cell possibly induced the more severe LPS-exhaustion and increased the infection susceptibility in FcGRIIb-/- mice. PMA induced PRKCB, improved LPS-tolerance, and attenuated sepsis severity, predominantly in FcGRIIb-/- mice. PRKCB enhancement might be a promising strategy to improve macrophage functions in lupus patients with LPS-tolerance from chronic infection.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
/
Receptores de IgG
/
Proteômica
/
Endotoxinas
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Proteína Quinase C beta
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Lúpus Eritematoso Sistêmico
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Macrófagos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Tailândia