Toll-like Receptor 4 (D8L5W) Rabbit mAb

Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor in Drosophila, play a pivotal role in innate immune responses (1-4). TLRs recognize conserved motifs found in various pathogens and mediate defense responses (5-7). Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes (4). The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the Toll/Interleukin-1 receptor (TIR) domain (1). Upon activation, TLRs associate with a number of cytoplasmic adapter proteins containing TIR domains, including myeloid differentiation factor 88 (MyD88), MyD88-adapter-like/TIR-associated protein (MAL/TIRAP), TIR domain-containing adapter-inducing IFN-β (TRIF), and Toll-receptor-associated molecule (TRAM) (8-10). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK (8,11-14). Activation of IKK leads to the degradation of IκB, which normally maintains NF-κB in an inactive state by sequestering it in the cytoplasm.TLR4 functions in association with MD-2 in the recognition and initiation of immune responses elicited by lipopolysaccharide (LPS) of Gram-negative bacteria (4-8). TLR4 triggers the activation of NF-κB, IRF-3, and MAPK pathways leading to the production of inflammatory cytokines (9). 1.Akira, S. (2003) J Biol Chem 278, 38105-8. 2.Beutler, B. (2004) Nature 430, 257-63. 3.Dunne, A. and O'Neill, L.A. (2003) Sci STKE 2003, re3. 4.Medzhitov, R. et al. (1997) Nature 388, 394-7. 5.Schwandner, R. et al. (1999) J Biol Chem 274, 17406-9. 6.Takeuchi, O. et al. (1999) Immunity 11, 443-51. 7.Alexopoulou, L. et al. (2001) Nature 413, 732-8. 8.Zhang, F.X. et al. (1999) J Biol Chem 274, 7611-4. 9.Horng, T. et al. (2001) Nat Immunol 2, 835-41. 10.Oshiumi, H. et al. (2003) Nat Immunol 4, 161-7. 11.Muzio, M. et al. (1997) Science 278, 1612-5. 12.Wesche, H. et al. (1997) Immunity 7, 837-47. 13.Suzuki, N. et al. (2002) Nature 416, 750-6. 14.Irie, T. et al. (2000) FEBS Lett 467, 160-4.