Runt-related Transcription Factor 1 (RUNX1) Binds to p50 in Macrophages and Enhances TLR4-triggered Inflammation and Septic Shock.
J Biol Chem
; 291(42): 22011-22020, 2016 Oct 14.
Article
em En
| MEDLINE
| ID: mdl-27573239
ABSTRACT
An appropriate inflammatory response plays critical roles in eliminating pathogens, whereas an excessive inflammatory response can cause tissue damage. Runt-related transcription factor 1 (RUNX1), a master regulator of hematopoiesis, plays critical roles in T cells; however, its roles in Toll-like receptor 4 (TLR4)-mediated inflammation in macrophages are unclear. Here, we demonstrated that upon TLR4 ligand stimulation by lipopolysaccharide (LPS), macrophages reduced the expression levels of RUNX1 Silencing of Runx1 attenuated the LPS-induced IL-1ß and IL-6 production levels, but the TNF-α levels were not affected. Overexpression of RUNX1 promoted IL-1ß and IL-6 production in response to LPS stimulation. Moreover, RUNX1 interacted with the NF-κB subunit p50, and coexpression of RUNX1 with p50 further enhanced the NF-κB luciferase activity. Importantly, treatment with the RUNX1 inhibitor, Ro 5-3335, protected mice from LPS-induced endotoxic shock and substantially reduced the IL-6 levels. These findings suggest that RUNX1 may be a new potential target for resolving TLR4-associated uncontrolled inflammation and preventing sepsis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Choque Séptico
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Transdução de Sinais
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Macrófagos Peritoneais
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Subunidade p50 de NF-kappa B
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Receptor 4 Toll-Like
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Subunidade alfa 2 de Fator de Ligação ao Core
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2016
Tipo de documento:
Article