TLR4 Antibody (HTA125) [Biotin]

TLR4 (Toll-like receptor 4) is a type-1 transmembrane glycoprotein that is a pattern recognition receptor (PRR) belonging to the TLR family (1-3). TLR4 is expressed in many tissues and is most abundantly expressed in the placenta, spleen, and peripheral blood leukocytes (1). Human TLR4 is synthesized as a 839 amino acid (aa) protein containing a signal sequence (1-23 aa), an extracellular domain (ECD) (24-631 aa), a transmembrane domain (632-652 aa), and Toll/interleukin-1 receptor (TIR) cytoplasmic domain (652-839 aa) with a theoretical molecular weight of 95 kDa (3, 4). The ECD contains 21 leucine-rich repeats (LRRs) and has a horseshoe-shaped structure (3, 4). TLR4 requires binding with the co-receptor myeloid differentiation protein 2 (MD2) largely via hydrophilic interactions for proper ligand sensing and signaling (2-4). In general, the TLR family plays a role in activation of innate immunity and responds to a variety of pathogen-associated molecular patterns (PAMPs) (5). TLR4 is specifically responsive to lipopolysaccharide (LPS), which is found on the outer-membrane of most ram-negative bacteria (3-5). Activation of TLR4 requires binding of a ligand, such as LPS to MD2, followed by MD2-LPS complex binding to TLR4, resulting in a partial complex (TLR4-MD2/LPS) (3, 5). To become fully active, two partial complexes must dimerize thereby allowing the TIR domains of TLR4 to bind other adapter molecular and initiate signaling, triggering an inflammatory response and cytokine production (3, 5).

TLR4 signaling occurs through two distinct pathways: The MyD88 (myeloid differentiation primary response gene 88)-dependent pathway and the MyD88-independent (TRIF-dependent, TIR domain-containing adaptor inducing IFN-beta) pathway (3, 5-7). The MyD88-dependent pathway occurs mainly at the plasma membrane and involves the binding of MyD88-adaptor-like (MAL) protein followed by a signaling cascade that results in the activation of transcription factors including nuclear factor-kappaB (NF-kappaB) that promote the secretion of inflammatory molecules and increased phagocytosis (5-7). Conversely, the MyD88-independent pathway occurs after TLR4-MD2 complex internalization in the endosomal compartment. This pathway involves the binding of adapter proteins TRIF and TRIF-related adaptor molecule (TRAM), a signaling activation cascade resulting in IFN regulatory factor 3 (IRF3) translocation into the nucleus, and secretion of interferon-beta (INF-beta) genes and increased phagocytosis (5-7).

Given its expression on immune-related cells and its role in inflammation, TLR4 activation can contribute to various diseases (6-8). For instance, several studies have found that TLR4 activation is associated with neurodegeneration and several central nervous system (CNS) pathologies, including Alzheimer's disease, Parkinson's disease, and Huntington's disease (6, 7). Furthermore, TLR4 mutations have been shown to lead to higher rates of infections and increased susceptibility to sepsis (7-8). One potential therapeutic approach aimed at targeting TLR4 and neuroinflammation is polyphenolic compounds which include flavonoids and phenolic acids and alcohols (8).

Alternative names for TLR4 includes 76B357.1, ARMD10, CD284 antigen, CD284, EC 3.2.2.6, homolog of Drosophila toll, hToll, toll like receptor 4 protein, TOLL, toll-like receptor 4.

References

1. Vaure, C., & Liu, Y. (2014). A comparative review of toll-like receptor 4 expression and functionality in different animal species. Frontiers in immunology. https://doi.org/10.3389/fimmu.2014.00316

2. Park, B. S., & Lee, J. O. (2013). Recognition of lipopolysaccharide pattern by TLR4 complexes. Experimental & molecular medicine. https://doi.org/10.1038/emm.2013.97

3. Krishnan, J., Anwar, M.A., & Choi, S. (2016) TLR4 (Toll-Like Receptor 4). In: Choi S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_592-1

4. Botos, I., Segal, D. M., & Davies, D. R. (2011). The structural biology of Toll-like receptors. Structure. https://doi.org/10.1016/j.str.2011.02.004

5. Lu, Y. C., Yeh, W. C., & Ohashi, P. S. (2008). LPS/TLR4 signal transduction pathway. Cytokine. https://doi.org/10.1016/j.cyto.2008.01.006

6. Leitner, G. R., Wenzel, T. J., Marshall, N., Gates, E. J., & Klegeris, A. (2019). Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders. Expert opinion on therapeutic targets. https://doi.org/10.1080/14728222.2019.1676416

7. Molteni, M., Gemma, S., & Rossetti, C. (2016). The Role of Toll-Like Receptor 4 in Infectious and Noninfectious Inflammation. Mediators of inflammation. https://doi.org/10.1155/2016/6978936

8. Rahimifard, M., Maqbool, F., Moeini-Nodeh, S., Niaz, K., Abdollahi, M., Braidy, N., Nabavi, S. M., & Nabavi, S. F. (2017). Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation. Ageing research reviews. https://doi.org/10.1016/j.arr.2017.02.004

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

We have publications tested in 1 confirmed species: Human.

We have publications tested in 3 applications: FLOW, Flow-CS, ICC/IF.

Showing Publications 1 - 10 of 18. Show All 18 Publications. Collapse Publications.

Publications using NBP2-24744	Applications	Species
Harman AN, Bye CR, Nasr N et al. Identification of lineage relationships and novel markers of blood and skin human dendritic cells. J Immunol. 2013-01-01 [PMID: 23183897] Details: Antibodies cited in Fig 4B for flow cytometric analysis of TLR expression in human monocyte-derived dendritic cells (MDDC), CD14+ monocytes, myeloid DC, and plasmacytoid DC:1. TLR2-FITC, clone T2.1 (IMG-416C): Flow (cell surface)2. TLR4-PE, clone HTA124 (
Matsunaga N, Tsuchimori N, Matsumoto T, Ii M. TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules. Mol Pharmacol. 2011-01-01 [PMID: 20881006]
Pillay J, Ramakers BP, Kamp VM et al. Functional heterogeneity and differential priming of circulating neutrophils in human experimental endotoxemia. J Leukoc Biol. 2010-07-01 [PMID: 20400675]
Wu CY, Chi PL, Hsieh HL et al. TLR4-dependent induction of vascular adhesion molecule-1 in rheumatoid arthritis synovial fibroblasts: Roles of cytosolic phospholipase A(2)alpha/cyclooxygenase-2. J Cell Physiol. 2010-05-01 [PMID: 20112284]
Pietschmann K, Beetz S, Welte S et al. Toll-like receptor expression and function in subsets of human gammadelta T lymphocytes. Scand J Immunol. 2009-09-01 [PMID: 19703014]
O'Hara Steven P, Small Aaron J, Gajdos Gabriella B et al. HIV-1 Tat protein suppresses cholangiocyte toll-like receptor 4 expression and defense against Cryptosporidium parvum. J Infect Dis. 2009-04-15 [PMID: 19265483]
Yang X, Fullerton DA, Su X et al Pro-osteogenic phenotype of human aortic valve interstitial cells is associated with higher levels of Toll-like receptors 2 and 4 and enhanced expression of bone morphogenetic protein 2. J Am Coll Cardiol. 2009-02-10 [PMID: 19195606] Details: Citation using the Azide Free version of this antibody.
Hammadi A, Billard C, Faussat AM et al. Stimulation of iNOS expression and apoptosis resistance in B-cell chronic lymphocytic leukemia (B-CLL) cells through engagement of Toll-like receptor 7 (TLR-7) and NF-kappaB activation. Nitric Oxide. 2008-09-01 [PMID: 18474259]
Burgener IA, Jungi TW. Antibodies specific for human or murine Toll-like receptors detect canine leukocytes by flow cytometry. Vet Immunol Immunopathol. 2008-07-15 [PMID: 18439687] Details: Canine (dog) PBMC subpopulations: 1. 10083K [IC-Flow (Intracellular Staining Flow Assay) Kit.
Prabha C, Rajashree P, Sulochana DD. TLR2 and TLR4 expression on the immune cells of tuberculous pleural fluid. Immunol Lett. 2008-04-15 [PMID: 18295348] Details: TLR2- FITC (IMG-416C): Flow (cell surface): Figs. 1A, B (human CD4+T cells, CD8+T cells, B cells, CD16+56+ cells and monocytes); 2(CD4+T cells); 4A, B (human Treg cells). Flow (intracellular): Fig. 3A, B (CD4+T cells) 2. TLR4- FITC (IMG-417C).Flow (cell surface): Figs. 1B, C (human CD4+T cells, CD8+T cells, B cells, CD16+56+ cells and monocytes); 2(CD4+T cells); 4A, B (human Treg cells). Flow (intracellular): Fig. 3A, B (CD4+T cells).
Pegu A, Qin S, Fallert Junecko BA et al. Human lymphatic endothelial cells express multiple functional TLRs. J Immunol. 2008-03-01 [PMID: 18292566] Details: Antibodies cited [Flow (Cell surface) and Flow (Intracellular), human lymphatic endothelial cells, Fig. 1D]: 1. IMG-663C (TLR5-FITC) 2. IMG-304C (TLR6-FITC).
Murciano C, Villamon E, Yanez A et al. In vitro response to Candida albicans in cultures of whole human blood from young and aged donors. FEMS Immunol Med Microbiol. 2007-11-01 [PMID: 17714490] Details: The following anitbodies were used in flow (cell surface) cytometry: TLR2/CD282 FITC (IMG-416C), TLR4 FITC (IMG-417C), TLR6/CD286 FITC (IMG-304C). Human whole blood from both young and elderly volunteers, Fig 1. Note: The fluorescence mean intensity was m
Wong CK, Cheung PF, Ip WK et al. Intracellular signaling mechanisms regulating toll-like receptor-mediated activation of eosinophils. Am J Respir Cell Mol Biol. 2007-07-01 [PMID: 17332440] Details: Human blood eosinophils and neutrophils from buffy coat: For WB, Fig. 1A: TLR1 (IMG-5012), TLR5 (IMG-664), TLR6 (IMG-304A), TLR7 (IMG-540), TLR8 (IMG-321A), TLR9 (IMG-305A). For Flow (Intracellular) and Flow (Surface), Fig. 1B: TLR1 (IMG-5021), TLR2 (IMG-416C), TLR3 (IMG-315C), TLR4 (IMG-417C), TLR5 (IMG-663C), TLR6 (IMG-304C), TLR7 (IMG-665A), TLR8 (IMG-321C), TLR9 (IMG-305C).
Basu S, Pathak SK, Banerjee A et al. Execution of macrophage apoptosis by PE_PGRS33 of Mycobacterium tuberculosis is mediated by Toll-like receptor 2-dependent release of tumor necrosis factor-alpha. J Biol Chem. 2007-01-12 [PMID: 17095513] (FLOW, Human)	FLOW	Human
Shahrara S, Park CC, Temkin V et al. RANTES modulates TLR4-induced cytokine secretion in human peripheral blood monocytes. J Immunol. 2006-10-15 [PMID: 17015691] (Flow-CS) Details: TLR4 (IMG-417A): Flow (Cell Surface) [PB monocytes], Fig. 2C.	Flow-CS
Scheel O, Papavlassopoulos M, Blunck R et al. Cell activation by ligands of the toll-like receptor and interleukin-1 receptor family depends on the function of the large-conductance potassium channel MaxiK in human macrophages. Infect Immun. 2006-07-01 [PMID: 16790810] (ICC/IF) Details: TLR4 (IMG-417A) [IF/ICC, Fig.3 (HEK293-TLR4/MD2-MaxiKGFP cells)].	ICC/IF
Konno K, Wakabayashi Y, Akashi-Takamura S et al. A molecule that is associated with Toll-like receptor 4 and regulates its cell surface expression. Biochem Biophys Res Commun. 2006-01-27 [PMID: 16338228]
Mempel M, Voelcker V, Kollisch G et al. Toll-like receptor expression in human keratinocytes: nuclear factor kappaB controlled gene activation by Staphylococcus aureus is toll-like receptor 2 but not toll-like receptor 4 or platelet activating factor receptor dependent. J Invest Dermatol. 2003-12-01 [PMID: 14675188] (ICC/IF, Human) Details: TLR2 (IMG-416) 2. TLR4 (IMG-417) [IF/ICC, Fig.2A and 2D (human keratinocytes)].	ICC/IF	Human
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Array NBP2-24744

• TLR4 Antibodies
• TLR4 ELISA Kits
• TLR4 Inhibitors
• TLR4 Lysate
• TLR4 Proteins
• TLR4 Proteins and Enzymes