Cytokines use different intracellular mechanisms to upregulate the membrane expression of CX3CR1 in human monocytes.
Mol Immunol
; 108: 23-33, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30776726
ABSTRACT
Membrane expression of fractalkine (CX3CL1)-receptor (CX3CR1) is relevant in monocytes (Mo) because CX3CR1-CX3CL1 interactions might participate on both, homeostatic and pathologic conditions. We have previously demonstrated that CX3CR1 levels are decreased during culture and when Mo are differentiated into dendritic cells, but enhanced when differentiated into macrophages. Regarding soluble factors, lipopolysaccharide (LPS) accelerated the loss of CX3CR1, while interleukin (IL)-10 and Interferon-gamma (IFN-γ) prevented it. However, the comprehensive knowledge about the intracellular pathways that underlay the level of CX3CR1 expression in Mo is still incomplete. In the current work, we studied the effect of anti-inflammatory cytokines (IL-4, IL-13, IL-10), alone or together with IFN- γ on CX3CR1 expression. We found that only IL-10 and IFN-γ separately were able to prevent CX3CR1 down-modulation during culture of human Mo. Besides, Mo incubated with IL-10 plus IFN-γ showed the highest CX3CR1 expression by cell, suggesting cooperation between two different mechanism used by both cytokines. By studying intracellular mechanisms triggered by IL-10 and IFN-γ, we demonstrated that they specifically induced PI3K-dependent serine-phosphorylation of signal transducer and activator of transcription (STAT)3 or STAT1, respectively. Moreover, chemical inhibitors of STAT1 or STAT3 abrogated IFN-γ or IL-10 effects on CX3CR1 expression. Strikingly, only IL-10 increased CX3CR1 mRNA level, as consequence of augmenting mRNA stability. CX3CR1 mRNA increase was PI3K-dependent, supporting the causal link between the action of IL-10 at the CX3CR1 transcript and CX3CR1 protein level on Mo. Thus, both cytokines up-regulate CX3CR1 expression on human Mo by different intracellular mechanisms.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Monócitos
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Regulação para Cima
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Interferon gama
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Interleucina-10
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Receptor 1 de Quimiocina CX3C
Limite:
Humans
Idioma:
En
Revista:
Mol Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Argentina