Tumor necrosis factor receptor 1 associates with CD137 ligand and mediates its reverse signaling.
FASEB J
; 27(8): 2957-66, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23620528
ABSTRACT
Reverse signaling through CD137 ligand (CD137L) potently activates monocytes. However, the underlying mechanism is not well elucidated. This study provides evidence that tumor necrosis factor receptor 1 (TNFR1) acts as a coreceptor for CD137L and mediates CD137L signaling. CD137L colocalizes with TNFR1 on the plasma membrane and binds directly to TNFR1 via its extracellular domain. Using the human monocytic THP-1 cell line, we demonstrate that engagement of CD137L by recombinant CD137 protein promotes cell adhesion, apoptosis, expression of CD14, and production of IL-8 and tumor necrosis factor (TNF). Concomitantly, the expression of TNFR1 protein is down-regulated in response to CD137L activation, due to enhanced extracellular release and internalization of TNFR1. Activation of TNFR1 by TNF protein additively augments CD137L-induced IL-8 expression. Conversely, inhibition of TNFR1 activity by a TNFR1-neutralizing antibody inhibits CD137L-mediated cell adhesion, cell death, CD14 expression, and IL-8 production. Taken together, these data show that TNFR1 associates with CD137L and is required for CD137L reverse signaling.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Monócitos
/
Transdução de Sinais
/
Receptores Tipo I de Fatores de Necrose Tumoral
/
Ligante 4-1BB
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Singapura