TLR4 Antibody - BSA Free

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 7 applications: FLOW, ICC/IF, IF/IHC, IHC-Fr, IHC-P, PLA, WB.

Showing Publications 1 - 10 of 16. Show All 16 Publications. Collapse Publications.

Publications using NB100-56581	Applications	Species
Riehl TE, Alvarado D, Ee X et al. Hyaluronic acid promotes Lgr5+ stem cell proliferation and crypt fission through TLR4 and PGE2 transactivation of EGFR Am. J. Physiol. Gastrointest. Liver Physiol. 2020-06-15 [PMID: 32538139]
Flores-Espinosa P, Pineda-Torres M, Vega-Sanchez R et al. Progesterone Elicits an Inhibitory Effect upon LPS-Induced Innate Immune Response in Pre-Labor Human Amniotic Epithelium. Am J Reprod Immunol. 2013-10-16 [PMID: 24128422] (ICC/IF, IHC-Fr, Human)	ICC/IF, IHC-Fr	Human
Lu Z, Li Y, Samuvel DJ, Jin J et al. MD-2 Is Involved in the Stimulation of MMP-1 Expression by IFNgamma and High Glucose in Mononuclear Cells - A Potential Role of MD-2 in TLR4-Independent Signaling. Immunology 2013-06-26 [PMID: 23800176] (FLOW, Human)	FLOW	Human
Li X, Kroin JS, Kc R et al. Altered spinal microRNA-146a and the microRNA-183 cluster contribute to osteoarthritic pain in knee joints. J Bone Miner Res 2013-06-06 [PMID: 23744481]
Cammarota R, Bertolini V, Pennesi G et al. The tumor microenvironment of colorectal cancer: stromal TLR-4 expression as a potential prognostic marker. J Transl Med. 2010-11-08 [PMID: 21059221] (IHC-P, Mouse)	IHC-P	Mouse
Burgueno, JF Understanding the role of Toll-like receptors in the lower gastrointestinal tract. Thesis. 2014-01-01 (IHC-P, Mouse) Details: Colon, Figs 1-3	IHC-P	Mouse
Arnaboldi F, Sommariva M, Opizzi E et al. Expression of Toll-like receptors 4 and 7 in murine peripheral nervous system development Ann. Anat. 2020-05-04 [PMID: 32380196] (IHC-P, Mouse)	IHC-P	Mouse
Barajon I, Serrao G, Arnaboldi F et al. Toll-like receptors 3, 4, and 7 are expressed in the enteric nervous system and dorsal root ganglia. J Histochem Cytochem. 2009-11-01 [PMID: 19546475] (WB, IF/IHC, Mouse) Details: TLR7 (IMG-581A). IHC (paraffin): Submucous plexus of murine intestine (Fig 1), murine small bowel (Fig 3), and myenteric plexus from human intestine (Fig 4). IF/ICC: Murine myenteric plexus, Fig 2.	WB, IF/IHC	Mouse
Carrithers M, Tandon S, Canosa S et al. Enhanced susceptibility to endotoxic shock and impaired STAT3 signaling in CD31-deficient mice. Am J Pathol. 2005-01-01 [PMID: 15632011] (WB, FLOW, Mouse) Details: 1. TLR4 (IMG-579A) [FACS analysis , FIG. 11 (mouse WT and CD31-deficient splenocytes and endothelial cells)].	WB, FLOW	Mouse
Jia R, Jia N, Yang F et al. Modification of primary amines to higher order amines reduces in vivo hematological and immunotoxicity of cationic nanocarriers through TLR4 and complement pathways bioRxiv (FLOW, Mouse)	FLOW	Mouse
Blanchard EL, Loomis KH, Bhosle SM et al. Proximity ligation assays for in situ detection of innate immune activation: focus on in vitro transcribed mRNA. Mol Ther Nucleic Acids. [PMID: 30579042] (PLA, Mouse)	PLA	Mouse
Takeo M, Nishio A, Masuda M Et al. Repeated Stimulation of Toll-Like Receptor 2 and Dectin-1 Induces Chronic Pancreatitis in Mice Through the Participation of Acquired Immunity Digestive diseases and sciences 2021-08-23 [PMID: 34424458]
Smith P, Godde N, Rubio S et al. Modification of primary amines to higher order amines reduces in vivo hematological and immunotoxicity of cationic nanocarriers through TLR4 and complement pathways Biomaterials 2019-10-05 [PMID: 31585233]
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
Herber DL, Maloney JL, Roth LM et al. Diverse microglial responses after intrahippocampal administration of lipopolysaccharide. Glia. 2006-03-01 [PMID: 16288481] (IF/IHC, Mouse) Details: IHC (F): Hippocampus from LPS-treated mice, Fig 1A, B, C.	IF/IHC	Mouse
Show All 16 Publications. Collapse Publications.

Images	Ratings	Applications	Species	Date	Details
	4 reviewed by: Lauren Shuman	IHC-P	Human	08/27/2014	View Summary Application Immunohistochemistry-Paraffin Sample Tested human inflammatory breast cancer Species Human

Array NB100-56581

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