TLR4 Antibody (MTS510) [PE]

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: Mouse.

We have publications tested in 4 applications: FLOW, Flow-CS, ICC/IF, WB.

Showing Publications 1 - 10 of 11. Show All 11 Publications. Collapse Publications.

Publications using NBP2-24741	Applications	Species
Tsai CC, Lin CR, Tsai HY et al. The immunologically active oligosaccharides isolated from wheatgrass modulate monocytes via Toll-like receptor-2 signaling J Biol Chem 2013-05-01 [PMID: 23629653]
Kim MY, Shu Y, Carsillo T et al. hsp70 and a novel axis of type I interferon-dependent antiviral immunity in the measles virus-infected brain. J Virol. 2013-01-01 [PMID: 23135720]
Ma CY, Shi GY, Shi CS et al. Monocytic thrombomodulin triggers LPS- and gram-negative bacteria-induced inflammatory response. J Immunol. 2012-06-15 [PMID: 22573811] (ICC/IF, Mouse) Details: TLR4 (IMG-428A). IF: mouse peritoneal macrophages (Fig 5D).	ICC/IF	Mouse
Bruscia EM, Zhang PX, Satoh A et al. Abnormal trafficking and degradation of TLR4 underlie the elevated inflammatory response in cystic fibrosis. J Immunol. 2011-06-15 [PMID: 21593379] Details: 1. TLR4/CD284 (IMG-428C) & TLR2/CD282 (IMG-6320C) : WB, IF/ICC, Flow (cell surface): Human macrophages with cystic fibrosis (CF) and wild type (WT) mouse macrophages, Fig 1 & S4. 2. TLR4/CD284 WB: CF and wild type macrophages treated with protein synthesi
Park HJ, Hong JH, Kwon HJ et al. TLR4-mediated activation of mouse macrophages by Korean mistletoe lectin-C (KML-C). Biochem Biophys Res Commun. 2010-06-04 [PMID: 20450885] (WB, Mouse) Details: The following antibodies were used: TLR4/CD284 (IMG-428E), TLR4/CD284 (IMG-577), and TLR4 (IMG-6307A). IMG-577 & IMG-6307A were used in Fig 1 (WB): Peritoneal primary mouse (BALB/C) macrophages stimulated with LPS and then treated with KML-C (Korean mistl	WB	Mouse
Tsukamoto H, Fukudome K, Takao S et al. Lipopolysaccharide-binding protein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells. Int Immunol. 2010-04-01 [PMID: 20133493] (WB) Details: TLR4 (IMG-578): WB, TLR4 stably transfected Ba/F3 cells. Note: These cells were immunoprecipitated with a TLR4 mAb (clone UT41) then western blotted with the IMG-578A TLR4 pAb Fig 3B. 3. TLR4 (IMG-428A): Flow (cell surface), RAW264 and TLR4 stably transfected Ba/F3 cells. Figs 1B, 1E.	WB
Macedo GC, Magnani DM, Carvalho NB et al. Central role of MyD88-dependent dendritic cell maturation and proinflammatory cytokine production to control Brucella abortus infection. J Immunol. 2008-01-15 [PMID: 18178848] (FLOW, Mouse) Details: IMG-428E: FA (mouse bone marrow derived and splenic dentritic cells), Fig. 7C,D.	FLOW	Mouse
Corbucci C, Cenci E, Skrzypek F et al. Immune response to Candida albicans is preserved despite defect in O-mannosylation of secretory proteins. Med Mycol. 2007-12-01 [PMID: 17885949] (Flow-CS) Details: Products cited (mouse macrophages): 1. IMG-428C (TLR4): Flow (Cell Surface), Fig. 5A 2. IMG-428E (TLR4): FA, Fig. 5B.	Flow-CS
El Shikh ME, El Sayed RM, Wu Y et al. TLR4 on follicular dendritic cells: an activation pathway that promotes accessory activity. J Immunol. 2007-10-01 [PMID: 17878340] Details: Products cited: 1. TLR4-FITC (IMG-428C): Flow (Cell Surface), Fig 1C, D [primary follicular dendritic (FDC) and B cells isolated from BALB/c mouse splenic leukocytes]. FDC cells expressed TLR4, but the B cells did not. 2. TLR4 (IMG-579A): IHC (F), Fig 1A
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]
Jung DY, Lee H, Jung BY et al. TLR4, but not TLR2, signals autoregulatory apoptosis of cultured microglia: a critical role of IFN-beta as a decision maker J Immunol 2005-05-10 [PMID: 15879150] (Flow-CS)	Flow-CS
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Array NBP2-24741

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