Author/Authors :
Duffy، نويسنده , , Karen E. and Lamb، نويسنده , , Roberta J. and San Mateo، نويسنده , , Lani R. and Jordan، نويسنده , , Jarrat L. and Canziani، نويسنده , , Gabriela and Brigham-Burke، نويسنده , , Michael and Korteweg، نويسنده , , Jeremy and Cunningham، نويسنده , , Mark and Beck، نويسنده , , Heena Solanki and Carton، نويسنده , , Jill and Giles-Komar، نويسنده , , Jill and Duchala، نويسنده , , Cynthia and Sarisky، نويسنده , , Robert T. and Mbow، نويسنده , , M. Lamine، نويسنده ,
Abstract :
Toll-like receptors are a family of pattern-recognition receptors that contribute to the innate immune response. Toll-like receptor 3 (TLR3) signals in response to foreign, endogenous and synthetic ligands including viral dsRNA, bacterial RNA, mitochondrial RNA, endogenous necrotic cell mRNA and the synthetic dsRNA analog, poly(I:C). We have generated a monoclonal antibody (mAb CNTO2424) that recognizes the extracellular domain (ECD) of human TLR3 in a conformation-dependent manner. CNTO2424 down-regulates poly(I:C)-induced production of IL-6, IL-8, MCP-1, RANTES, and IP-10 in human lung epithelial cells. In addition, mAb CNTO2424 was able to interfere with the known TLR3-dependent signaling pathways, namely NF-κB, IRF-3/ISRE, and p38 MAPK. The generation of this neutralizing anti-TLR3 mAb provides a unique tool to better understand TLR3 signaling and potential cross-talk between TLR3 and other molecules.
Keywords :
Toll-like receptor 3 , innate immunity , monoclonal antibody , TLR , TLR3 , Poly(I:C)
