TLR4 Antibody

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 2 confirmed species: Human, Mouse.

We have publications tested in 2 applications: IP, WB.

Showing Publications 1 - 10 of 12. Show All 12 Publications. Collapse Publications.

Publications using NB100-56579	Applications	Species
Liang Zhou, Lei Fang, Michael Roth, Eleni Papakonstantinou, Michael Tamm, Daiana Stolz Heat-Induced Secretion of Heat Shock Proteins 70 and 90 Does not Affect the Expression of the Glucocorticoid Receptor in Primary Airway Cells in COPD Lung 2024-04-19 [PMID: 38641747]
Cho D, Zhang S, Lazrak A et al. LPS DECREASES CFTR OPEN PROBABILITY AND MUCOCILIARY TRANSPORT THROUGH GENERATION OF REACTIVE OXYGEN SPECIES Redox Biology 2021-04-01 [PMID: 33971543] (WB, Mouse)	WB	Mouse
Oka SI, Byun J, Huang CY, Imai N, Ralda G, Zhai P, Xu X, Kashyap S, Warren JS, Alan Maschek J, Tippetts TS, Tong M, Venkatesh S, Ikeda Y, Mizushima W, Kashihara T, Sadoshima J. Nampt Potentiates Antioxidant Defense in Diabetic Cardiomyopathy 2021-04-30 [PMID: 33928788] (WB, Mouse)	WB	Mouse
Moreth K, Frey H, Hubo M et al. Biglycan-triggered TLR-2- and TLR-4-signaling exacerbates the pathophysiology of ischemic acute kidney injury. Matrix Biol. 2014-01-28 [PMID: 24480070] (WB, Mouse) Details: Murine peritoneal macrophages, Fig 1C. Cells were IPd with biglycan, followed by WB with the TLR2 pAb. The IP/WB results showed that that TLR2 co-IPd with biglycan, indicating protein-protein interactions between biglycan and TLR2. TLR2 was detected at 90	WB	Mouse
Jin Yingji, Tachibana Isao, Takeda Yoshito et al. Statins decrease lung inflammation in mice by upregulating tetraspanin CD9 in macrophages. PLoS One. 2013-01-01 [PMID: 24040034] (WB, Mouse)	WB	Mouse
Krishnan S, Chen S, Turcatel G et al. Regulation of Toll-like receptor 2 interaction with Ecgp96 controls Escherichia coli K1 invasion of brain endothelial cells Cell Microbiol. 2013-01-01 [PMID: 22963587] (WB, Human)	WB	Human
Merline Rosetta, Moreth Kristin, Beckmann Janet et al. Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21. Sci Signal. 2011-01-01 [PMID: 22087031] (IP)	IP
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
Bansal K, Elluru SR, Narayana Y et al. PE_PGRS antigens of Mycobacterium tuberculosis induce maturation and activation of human dendritic cells. J Immunol. 2010-04-01 [PMID: 20176745] (WB) Details: The following antibodies were used for WB in Fig 4B, 4C using HEK-293 cells transiently transfected with TLR2 or TLR2 dominant negative constructs: 1. TLR1 (IMG-5012), 2. TLR2 IMG-(6320A), 3. TLR4 (IMG-577), 4.TLR6 (IMG-527).Note: TLR2 was transfected validated in Fig 4B.	WB
Suzuki Mayumi, Tachibana Isao, Takeda Yoshito et al. Tetraspanin CD9 negatively regulates lipopolysaccharide-induced macrophage activation and lung inflammation. J Immunol. 2009-05-15 [PMID: 19414803] (Mouse)		Mouse
Gandhi Shiv K, Siliciano Janet D, Bailey Justin R et al. Role of APOBEC3G/F-mediated hypermutation in the control of human immunodeficiency virus type 1 in elite suppressors. J Virol. 2008-03-01 [PMID: 18077705]
Ueta M, Nochi T, Jang MH et al. Intracellularly expressed TLR2s and TLR4s contribution to an immunosilent environment at the ocular mucosal epithelium. J Immunol. 2004-09-01 [PMID: 15322197] (IP) Details: 1. TLR4 (IMG-577) [IP, see results section].	IP
Show All 12 Publications. Collapse Publications.

Images	Ratings	Applications	Species	Date	Details
Enlarge	5 reviewed by: Shinichi Oka	WB	Mouse	09/09/2019	View Summary Application Western Blot Sample Tested Heart lysates Species Mouse Lot 0227024-11
	5 reviewed by: Verified Customer	WB	Human	12/12/2014	View Summary Application Western Blot Sample Tested See PMID 22963587 Species Human

Array NB100-56579

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