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 4 confirmed species: Human, Mouse, Rat, Primate (Rhesus monkey).

We have publications tested in 8 applications: Block/Neutralize, ICC/IF, IF/IHC, IHC-P, Immunohistochemistry, PLA, WB, Western Blot.

Showing Publications 1 - 10 of 27. Show All 27 Publications. Collapse Publications.

Publications using NB100-56580	Applications	Species
Niskanen J, Peltonen S, Ohtonen S et al. Uptake of alpha-synuclein preformed fibrils is suppressed by inflammation and induces an aberrant phenotype in human microglia. Glia 2024-10-22 [PMID: 39435593]
Chiara Barisione, Daniela Verzola, Silvano Garibaldi, Paola Altieri, Anna Lisa Furfaro, Mariapaola Nitti, Giovanni Pratesi, Domenico Palombo, Pietro Ameri Indoxyl sulphate‐initiated activation of cardiac fibroblasts is modulated by aryl hydrocarbon receptor and nuclear factor‐erythroid‐2‐related factor 2 Journal of Cellular and Molecular Medicine 2024-03-20 [PMID: 38506079]
Xinshuang ZOU, Lei SHI, Hailong YIN, Haiping LI, Mengheng WANG, Wanci SONG, Laichun LUO, Hezhen WU, Yanfang YANG, Junfeng ZAN, Yanwen LIU, Hanxiong DAN, Qiang YIN, Pengtao YOU Compound Gaoziban tablet (复方高滋斑片) alleviates depression via toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway Journal of Traditional Chinese Medicine 2022-09-02 [PMID: 36378054]
Hu D, Wang Y, You Z et al. lnc-MRGPRF-6:1 Promotes M1 Polarization of Macrophage and Inflammatory Response through the TLR4-MyD88-MAPK Pathway Mediators of inflammation 2022-01-28 [PMID: 35125964] (WB, Human)	WB	Human
Chaumonnot K, Masson S, Sikner H, et al. The HSP GRP94 interacts with macrophage intracellular complement C3 and impacts M2 profile during ER stress Cell death & disease 2021-01-22 [PMID: 33483465] (PLA, Human)	PLA	Human
Xu X, Su Y, Wu K et al. DOCK2 contributes to endotoxemia-induced acute lung injury in mice by activating proinflammatory macrophages Biochemical pharmacology 2020-12-28 [PMID: 33382969]
Li G, Makar T, Gerzanich V et al. HIV-1 Vpr-Induced Proinflammatory Response and Apoptosis Are Mediated through the Sur1-Trpm4 Channel in Astrocytes mBio 2020-12-22 [PMID: 33293383] (Immunohistochemistry, Western Blot, Block/Neutralize)	Immunohistochemistry, Western Blot, Block/Neutralize
Alanazi AM, Fadda L, Alhusaini A et al. Liposomal Resveratrol and/or Carvedilol Attenuate Doxorubicin-Induced Cardiotoxicity by Modulating Inflammation, Oxidative Stress and S100A1 in Rats Antioxidants (Basel) 2020-02-16 [PMID: 32079097] (IF/IHC, Rat)	IF/IHC	Rat
Koh GY, Kane A, Lee K et al. Parabacteroides distasonis attenuates toll-like receptor 4 signaling and Akt activation and blocks colon tumor formation in high-fat diet-fed azoxymethane-treated mice Int. J. Cancer 2018-04-26 [PMID: 29696632] (WB, Mouse)	WB	Mouse
Perconti G, Maranto C, Romancino DP et al. Pro-invasive stimuli and the interacting protein Hsp70 favour the route of alpha-enolase to the cell surface. Sci Rep. 2017-06-19 [PMID: 28630480] (ICC/IF, Human)	ICC/IF	Human
Compare D, Rocco A, Coccoli P et al. Lactobacillus casei DG and its postbiotic reduce the inflammatory mucosal response: an ex-vivo organ culture model of post-infectious irritable bowel syndrome. BMC Gastroenterol. 2017-04-14 [PMID: 28410580] (WB, Human)	WB	Human
Deiuliis JA, Syed R, Duggineni D et al. Visceral Adipose MicroRNA 223 Is Upregulated in Human and Murine Obesity and Modulates the Inflammatory Phenotype of Macrophages. PLoS ONE. 2016-11-04 [PMID: 27812198] (WB, Mouse)	WB	Mouse
Oyama JI, Shiraki A, Nishikido T et al. EGCG, a green tea catechin, attenuates the progression of heart failure induced by the heart/muscle-specific deletion of MnSOD in mice. J Cardiol 2016-06-30 [PMID: 27374189] (WB, Human)	WB	Human
Merkowsky K, Sethi RS, Gill JP, Singh B. Fipronil induces lung inflammation in vivo and cell death in vitro. J Occup Med Toxicol. 2016-03-21 [PMID: 26997970] (IHC-P, Mouse)	IHC-P	Mouse
Pahwa R, Devaraj S, Jialal I. The effect of the accessory proteins, soluble CD14 and lipopolysaccharide-binding protein on Toll-like receptor 4 activity in human monocytes and adipocytes. Int J Obes (Lond) 2016-06-01 [PMID: 26880233]
Riehl TE, Santhanam S, Foster L et al. CD44 and TLR4 mediate hyaluronic acid regulation of Lgr5+ stem cell proliferation, crypt fission, and intestinal growth in postnatal and adult mice. Am J Physiol Gastrointest Liver Physiol 2015-12-01 [PMID: 26505972] (Mouse)		Mouse
Duan H, Qu L, Shou C. Mycoplasma hyorhinis induces epithelial-mesenchymal transition in gastric cancer cell MGC803 via TLR4-NF-kappaB signaling. Cancer Lett 2014-11-28 [PMID: 25149064]
Balamurugan Kuppusamy, Sharan Shikha, Klarmann Kimberly D et al. FBXW7alpha attenuates inflammatory signalling by downregulating C/EBPdelta and its target gene Tlr4. Nat Commun. 2013-01-01 [PMID: 23575666]
Yokoyama R, Itoh S, Kamoshida G et al. Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor 2 extracellular domain and inhibits cytokine production induced by Staphylococcus aureus, cell wall component, or lipopeptides in murine macrophages. Infect Immun. 2012-08-01 [PMID: 22665377]
Oyama JI, Maeda T, Sasaki M et al. Repetitive hyperthermia attenuates progression of left ventricular hypertrophy and increases telomerase activity in hypertensive rats. Am J Physiol Heart Circ Physiol. 2012-03-16 [PMID: 22427516] (Rat)		Rat
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
Bernardino AL, Myers TA, Alvarez X et al. Toll-like receptors: insights into their possible role in the pathogenesis of lyme neuroborreliosis. Infect Immun. 2008-10-01 [PMID: 18694963] (ICC/IF, Primate (Rhesus monkey)) Details: IF (primary glial cell cultures from the brains of adult rhesus monkeys), Fig 5D&H. TLR4 expression increased following B burgdorferi infection.	ICC/IF	Primate (Rhesus monkey)
Shimada M, Yanai Y, Okazaki T et al. Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization. Development. 2008-06-01 [PMID: 18434414]
Gupta N, Su X, Popov B et al. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007-08-01 [PMID: 17641052] (WB, Mouse) Details: WB (Fig 9B): mouse bone-marrow derived primary mensenchymal stem cells and RAW cells. TLR4 was detected at ~90 kDa.	WB	Mouse
Bondeva T, Roger T, Wolf G. Differential regulation of Toll-like receptor 4 gene expression in renal cells by angiotensin II: dependency on AP1 and PU.1 transcriptional sites. Am J Nephrol. 2007-01-01 [PMID: 17495427] (WB, Mouse) Details: WB (Fig 2): mouse kidney derived cells (immortalized podocytes, cortical tubule cell line, mesiangial cell line).	WB	Mouse
Zager RA, Johnson AC, Lund S, Randolph-Habecker J. Toll-like receptor (TLR4) shedding and depletion: acute proximal tubular cell responses to hypoxic and toxic injury. Am J Physiol Renal Physiol. 2007-01-01 [PMID: 16885150] (WB) Details: WB (mouse renal cortex and urinary samples): Figs 2, 5, 6, 8. Note: TLR4 was observed at the following molecular weights: 1. Two ~90 kDa bands reflecting different degrees of TLR4 glycosylation (Fig 5A) 2. 30 kDA in postischemic urine samples, reflecting	WB
Zager RA, Johnson AC, Lund S, Hanson S. Acute renal failure: determinants and characteristics of the injury-induced hyperinflammatory response. Am J Physiol Renal Physiol. 2006-09-01 [PMID: 16638912] (WB, Human, Mouse) Details: 1. TLR4 (IMG-578) [WB, Fig. 10 (mouse kidney tissue, human kidney Hk-2 cell line)].	WB	Human, Mouse
Show All 27 Publications. Collapse Publications.

Images	Ratings	Applications	Species	Date	Details
Enlarge	3 reviewed by: Verified Customer	WB	Human	09/06/2017	View Summary Application Western Blot Sample Tested Neutrophilic cells whole cell lysate Species Human Lot AB011304B-13

Array NB100-56580

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