Down modulation of human TLR3 function by a monoclonal antibody.
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-kappaB, 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.
Discovery Research, Centocor Research and Development, Inc., Malvern, PA 19355, USA. kduffy@cntus.jnj.com
Karen E
KE
Duffy
Roberta J
RJ
Lamb
Lani R
LR
San Mateo
Jarrat L
JL
Jordan
Gabriela
G
Canziani
Michael
M
Brigham-Burke
Jeremy
J
Korteweg
Mark
M
Cunningham
Heena Solanki
HS
Beck
Jill
J
Carton
Jill
J
Giles-Komar
Cynthia
C
Duchala
Robert T
RT
Sarisky
M Lamine
ML
Mbow
D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001666:Binding Sites, Antibody; D002460:Cell Line; D002461:Cell Line, Transformed; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010865:Pilot Projects; D051196:Toll-Like Receptor 3 / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3