The mammalian host defense system is essentially regulated by highly conserved Toll-like receptor (TLR) family of proteins. At least 13 TLRs have been identified and cloned in mammalian cells which recognize molecular products/signals from all the major classes of pathogens and activation of innate immunity. The Toll signaling to NF-Kb starts form conserved Toll-IL-1-resistance (TIR) domain, which mediated the coupling of TIR adaptor molecules (MyD88, Mal, TICAM and TRAM) and caused production of inflammatory cytokines such as IL-1, IL-6, IL-8 , TNFa, and IL-12, chemokines and co-stimulatory molecules such as CD40, CD80 and CD86. In the presence of inflammatory cytokines and binding of adaptor molecule, MyD88 that binds FADD and triggers apoptosis through the caspase cascade. TLR induced apoptosis pathway appears to be a repertoire of defense mechanism utilized by innate defense mechanism. The constitutive expression of many human TLRs (1, 2, 3) have been shown on the surface of myeloid lineage cells by RT-PCR and use of specific monoclonal antibodies. Upon activation of these receptors by their respective chemokines and ligands have been shown in literature on various cell lines including endothelial, epithelial and other cells. The expression of TLR 3, 7, 8 and 9 are mainly found on endosomal lysosomal compartments. Human TLR3 is expressed in human fibroblasts cells and TLR 9 in in-vitro derived DC cells. There is significant evidence of TLR involvement is many systemic disorders following bacterial infection including sepsis, peridontitis, cardiac ischemia, cerebral palsy and others, understanding the TLRs involvement in these conditions will allow therapeutic interventions at the receptor level for treatment of these disorders.
The TLR are highly conserved protein and share structural and functional domains across species. These receptors recognize pathogen associated molecular patters (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines needed for production of immediate immunity. TLR4 signaling pathway are associated with expression of pro-inflammatory cytokines and activation of the PI3K/Akt signaling pathway in the hippocampal formation and is involved in ischemia-induced perfusion hippocampal neuronal death (4). Human TLR4 is a 839 amino acid (105 kDa) type I trans-membrane receptor protein characterized by extracellular domains with leucine-rich repeats and a cytoplasmic domain with type I IL-1 receptor. TLR4 deficiency led to the upregulation of what we believe to be a novel NADPH oxidase (Nox), Nox3, in lungs and endothelial cells, resulting in increased oxidant generation and elastolytic activity (5). The TLR 2 and 4 are pattern recognition receptors and signaling molecules in response to bacterial lipoproteins and is involved in innate immunity. TLR4 is expressed on peripheral blood and together with MD-2 and CD14 is responsible for LPS signaling recognition. Many specific adapter molecules (TICAM, MyD88, ICAM2, TRAM, TIRAP, TRIF etc) are also involved in signaling of several other TLRs.
The TLR 4-selective antibodies were generated against peptide form unique region near the C-terminal end of Toll receptor-4 protein, this peptide sequence is not present in other members of theTLR family. FabGennix Inc. has generated rabbit anti-TLR4 mono-epitope-specific antibodies utilizing linear and cyclic peptide methodology. The Anti-TLR4 antibodies have been fully characterized for cross reactivity with other members of the TLR family molecules and with cellular proteins using Western blot analyses. The TLR4 antibody is also available as FITC-conjugate, other conjugates can be ordered at a nominal charge. FabGennix International Inc., has produced antibodies to all Toll receptors (TLR1-TLR13), these antibodies are now available for sale from us or from our distributors. FabGennix Int. Inc., also provide western blot positive controls for TLR4 in ready-to-use buffer. Limited quantities of the antigenic blocking peptide for TLR4 antibodies is also available (inquire for availability).
For research use only, not for diagnostic or therapeutic use.
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