Overexpression of HMGB1 A-box reduced lipopolysaccharide-induced intestinal inflammation via HMGB1/TLR4 signaling in vitro.
World J Gastroenterol
; 21(25): 7764-76, 2015 Jul 07.
Article
em En
| MEDLINE
| ID: mdl-26167076
ABSTRACT
AIM:
To investigate the inhibitory effects and mechanism of high mobility group box (HMGB)1 A-box in lipopolysaccharide (LPS)-induced intestinal inflammation.METHODS:
Overexpression of HMGB1 A-box in human intestinal epithelial cell lines (SW480 cells) was achieved using the plasmid pEGFP-N1. HMGB1 A-box-overexpressing SW480 cells were stimulated with LPS and co-culturing with human monocyte-like cell lines (THP-1 cells) using a Transwell system, compared with another HMGB1 inhibitor ethyl pyruvate (EP). The mRNA and protein levels of HMGB1/toll-like receptor (TLR) 4 signaling pathways [including HMGB1, TLR4, myeloid differentiation factor88 (MYD88), Phosphorylated Nuclear Factor κB (pNF-κB) p65] in the stimulated cells were determined by real-time polymerase chain reaction and Western blotting. The levels of the proinflammatory mediators [including HMGB1, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α] in the supernatants of the stimulated cells were determined by ELISA.RESULTS:
EP downregulated the mRNA and protein levels of HMGB1, inhibited the TLR4 signaling pathways (TLR4, MYD88 and pNF-κB p65) and reduced the secretion of proinflammatory mediators (HMGB1, IL-1ß, IL-6 and TNF-α) in the SW480 and THP-1 cells activated by LPS but not in the unstimulated cells. Activated by LPS, the overexpression of HMGB1 A-box in the SW480 cells also inhibited the HMGB1/TLR4 signaling pathways and reduced the secretion of these proinflammatory mediators in the THP-1 cells but not in the transfected and unstimulated cells.CONCLUSION:
HMGB1 A-box, not only EP, can reduce LPS-induced intestinal inflammation through inhibition of the HMGB1/TLR4 signaling pathways.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Lipopolissacarídeos
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Mediadores da Inflamação
/
Proteína HMGB1
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Receptor 4 Toll-Like
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Gastroenterite
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Mucosa Intestinal
Limite:
Humans
Idioma:
En
Revista:
World J Gastroenterol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2015
Tipo de documento:
Article