Down modulation of human TLR3 function by a monoclonal antibody
| Autor: | Jeremy Korteweg, Jill Carton, Mark Cunningham, Michael Brigham-Burke, Heena Beck, M. Lamine Mbow, Jill Giles-Komar, Roberta J. Lamb, Robert T. Sarisky, Jarrat Jordan, Lani San Mateo, Karen E. Duffy, Cynthia Duchala, Gabriela Canziani |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.drug_class
viruses Immunology Pilot Projects chemical and pharmacologic phenomena Endogeny Biology Monoclonal antibody Cell Line Mice medicine Animals Humans Antibodies Blocking Receptor Cell Line Transformed Mice Inbred BALB C Messenger RNA Innate immune system Antibodies Monoclonal virus diseases hemic and immune systems Molecular biology Toll-Like Receptor 3 RNA silencing TLR3 Female Binding Sites Antibody Signal transduction |
| Zdroj: | Cellular Immunology. 248:103-114 |
| ISSN: | 0008-8749 |
| DOI: | 10.1016/j.cellimm.2007.10.002 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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