Neutralization of pro-inflammatory monocytes by targeting TLR2 dimerization ameliorates colitis.
EMBO J
; 35(6): 685-98, 2016 Mar 15.
Article
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
Colitis
/
Colon
/
Toll-Like Receptor 2
/
Protein Multimerization
Limits:
Animals
Language:
En
Journal:
EMBO J
Year:
2016
Type:
Article
Affiliation country:
Israel