1. Neutralization of pro‐inflammatory monocytes by targeting TLR2 dimerization ameliorates colitis
- Author
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Batya Zarmi, Biana Bernshtein, Avner Fink, Steffen Jung, Liraz Shmuel-Galia, Tegest Aychek, Ori Brenner, Yechiel Shai, and Ziv Porat
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Colon ,MAP Kinase Signaling System ,Inflammation ,Biology ,Monocytes ,General Biochemistry, Genetics and Molecular Biology ,Immunophenotyping ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Antigens, Ly ,Colitis ,Receptor ,Molecular Biology ,Toll-like receptor ,General Immunology and Microbiology ,Kinase ,General Neuroscience ,Interleukin ,Articles ,medicine.disease ,Toll-Like Receptor 2 ,3. Good health ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,TLR2 ,Toll-Like Receptor 6 ,030104 developmental biology ,Immunology ,Cytokines ,Protein Multimerization ,medicine.symptom ,030215 immunology - 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‐1β. 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.
- Published
- 2016
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