Neutralization of pro-inflammatory monocytes by targeting TLR2 dimerization ameliorates colitis.
EMBO J
; 35(6): 685-98, 2016 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-26884587
ABSTRACT
Monocytes have emerged as critical driving force of acute inflammation. Here, we show that inhibition of Toll-like receptor 2(TLR2) dimerization by a TLR2 transmembrane peptide (TLR2-p) ameliorated DSS-induced colitis by interfering specifically with the activation of Ly6C(+) monocytes without affecting their recruitment to the colon. We report that TLR2-p directly interacts with TLR2 within the membrane, leading to inhibition of TLR2-TLR6/1 assembly induced by natural ligands. This was associated with decreased levels of extracellular signal-regulated kinases (ERK) signaling and reduced secretion of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-23, IL-12, and IL-1ß. Altogether, our study provides insights into the essential role of TLR2 dimerization in the activation of pathogenic pro-inflammatory Ly6C(hi) monocytes and suggests that inhibition of this aggregation by TLR2-p might have therapeutic potential in the treatment of acute gut inflammation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Monócitos
/
Colite
/
Colo
/
Receptor 2 Toll-Like
/
Multimerização Proteica
Limite:
Animals
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Israel