TLR4 Inhibitor Peptide Set

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. Inhibitors are guaranteed for 1 year from date of receipt.

We have publications tested in 3 confirmed species: Human, Mouse, Rat.

We have publications tested in 9 applications: B/N, BindInhib, FLOW, Forced Spectroscopy, Func, In Vivo, In vitro, In-vitro, In-vivo.

Showing Publications 1 - 10 of 47. Show All 47 Publications. Collapse Publications.

Publications using NBP2-26244	Applications	Species
Verma S, Reddy P, Sowdhamini R Integrated approaches for the recognition of small molecule inhibitors for Toll-like receptor 4 Computational and Structural Biotechnology Journal 2023-07-22 [PMID: 37576745] (In vitro)	In vitro
Yang D, Dai X, Xing Y et al. Intrinsic cardiac adrenergic cells contribute to LPS-induced myocardial dysfunction Communications biology 2022-01-25 [PMID: 35079095]
Yamamoto K, Kondo Y, Ohnishi S Et al. The TLR4-TRIF-type 1 IFN-IFN- gamma pathway is crucial for gastric MALT lymphoma formation after Helicobacter suis infection iScience 2021-08-01 [PMID: 34585114] (In vitro)	In vitro
Gergen AK, Jarrett MJ, Li A et al. Toll-like Receptor 4 Mediates Reflux-Induced Inflammation in a Murine Reflux Model Seminars in thoracic and cardiovascular surgery 2021-09-14 [PMID: 34534678]
Mizuno Y, Taguchi T Self-assembled dodecyl group-modified gelatin microparticle-based hydrogels with angiogenic properties NPG Asia Mater 2020-12-01
Li B, Yan C, Wu J et al. Clonorchis sinensis ESPs enhance the activation of hepatic stellate cells by a cross-talk of TLR4 and TGF-beta/Smads Signaling pathway Acta Trop. 2019-12-17 [PMID: 31862462] (Func)	Func
Harada Y, Zhang J, Imari K et al. Cathepsin E in neutrophils contributes to the generation of neuropathic pain in experimental autoimmune encephalomyelitis Pain 2019-09-01 [PMID: 31095099] (Mouse)		Mouse
Chehimi M, Ward R, Pestel J et al. Omega-3 Polyunsaturated Fatty Acids Inhibit IL-17A Secretion through Decreased ICAM-1 Expression in T Cells Co-Cultured with Adipose-Derived Stem Cells Harvested from Adipose Tissues of Obese Subjects Mol Nutr Food Res 2019-03-08 [PMID: 30848861] (B/N, Human)	B/N	Human
Tun X, Yasukawa K, Yamada KI. Nitric Oxide Is Involved in Activation of Toll-Like Receptor 4 Signaling through Tyrosine Nitration of Src Homology Protein Tyrosine Phosphatase 2 in Murine Dextran Sulfate-Induced Colitis Biol. Pharm. Bull. 2018-12-04 [PMID: 30504685] (B/N, Mouse)	B/N	Mouse
Nishida M, Saegusa J, Tanaka S, Morinobu A. S100A12 facilitates osteoclast differentiation from human monocytes. PLoS ONE 2018-09-20 [PMID: 30235276] (Human)		Human
Alvarez D, Das B, Garcia-Mesa Y et al. The NCOR2-Nurr1-CoREST Transrepression Axis Impairs HIV Reactivation in Latently Infected Microglial Cells Conference on Retroviruses and Opportunistic Infections (CROI) 2014. (FLOW, Func, Human) Details: TLR4 Inhibitor used at 20uM concentration on Microglial/HIV Cells - CHME-5/HIV and hT-HMucroglia/HIV cells were untreated or treated with IL-1 beta (100 pg/mL), Pam3CSK4 (0.1 ug/mL), or a combination of IL-1 beta and Pam3CSK4 for 16 h prior to measuring GFP-expressing cells by FLOW (Fig 4B). COBRA, but not of VIPER, abolished the effect of Pam3CSK4, but not of IL-1 beta indicating that Pam3CSK4 is indeed responsible for the potentiation of HIV reactivation	FLOW, Func	Human
Mempin M, Hu H, Vickery K et al. Gram-Negative Bacterial Lipopolysaccharide Promotes Tumor Cell Proliferation in Breast Implant-Associated Anaplastic Large-Cell Lymphoma Cancers (Basel) 2021-10-22 [PMID: 34771464]
Sahoo SS, Pratheek BM, Meena VS et al. VIPER regulates naive T cell activation and effector responses: Implication in TLR4 associated acute stage T cell responses Sci Rep 2018-05-08 [PMID: 29740052] (B/N, Mouse)	B/N	Mouse
Li Q, Dai C, Xue R et al. S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic ApoptosisviaTLR4-ERK1/2 Signaling. Front Immunol. 2018-03-05 [PMID: 29556233] (B/N)	B/N
Inoue H, Shirakawa J, Togashi Y et al. Signaling between pancreatic B-cells and macrophages via S100 calcium-binding protein A8 exacerbates B-cell apoptosis and islet inflammation. J. Biol. Chem. 2018-03-01 [PMID: 29496993] (B/N)	B/N
Carnevale R, Nocella C, Petrozza V et al. Localization of lipopolysaccharide from Escherichia Coli into human atherosclerotic plaque. Sci Rep. 2018-02-26 [PMID: 29483584] (Human)		Human
Ohtsu A, Shibutani Y, Seno K et al. Advanced glycation end products and lipopolysaccharides stimulate interleukin-6 secretion via the RAGE/TLR4-NF-kB-ROS pathways and resveratrol attenuates these inflammatory responses in mouse macrophages. Exp Ther Med. 2017-11-01 [PMID: 29067115] (B/N, Mouse)	B/N	Mouse
Kato K, Hanss AD, Zemskova MA et al. Pseudomonas aeruginosa increases MUC1 expression in macrophages through the TLR4-p38 pathway Biochem. Biophys. Res. Commun. 2017-08-16 [PMID: 28822766] (B/N)	B/N
Nishikawa Y, Kajiura Y, Lew JH et al. Calprotectin Induces IL-6 and MCP-1 Production via Toll-Like Receptor 4 Signaling in Human Gingival Fibroblasts. J. Cell. Physiol. 2016-12-07 [PMID: 27925202] (B/N, Human)	B/N	Human
Hirai M, Kitahara H, Kobayashi Y et al. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment. Int. J. Oncol. 2017-01-01 [PMID: 27922697] (Func, Human)	Func	Human
Verzola D, Bonanni A, Sofia A et al. Toll-like receptor 4 signalling mediates inflammation in skeletal muscle of patients with chronic kidney disease. J Cachexia Sarcopenia Muscle. 2017-02-01 [PMID: 27897392] (BindInhib, Human)	BindInhib	Human
Estruch M, Sanchez-Quesada JL, Ordonez-Llanos J, Benitez S. Inflammatory intracellular pathways activated by electronegative LDL in monocytes. Biochim. Biophys. Acta. 2016-05-25 [PMID: 27235719]
Shirasuna K, Seno K, Ohtsu A et al. AGEs and HMGB1 Increase Inflammatory Cytokine Production from Human Placental Cells, Resulting in an Enhancement of Monocyte Migration. Am. J. Reprod. Immunol. 2016-05-01 [PMID: 26961863] (Func, Human)	Func	Human
Takahashi M, Chen-Yoshikawa TF, Menju T. Inhibition of Toll-like Receptor 4 Signaling Ameliorates Lung Ischemia-reperfusion Injury in Acute Hyperglycemic Conditions. J Heart Lung Transplant. 2016-01-22 [PMID: 26922276]
Wei W, Xiao HT, Bao WR et al. TLR-4 may mediate signaling pathways of Astragalus polysaccharide RAP induced cytokine expression of RAW264.7 cells. J Ethnopharmacol. 2015-12-29 [PMID: 26743224]
Guo J, Zheng L, Chen L et al. Lipopolysaccharide activated TLR4/NF-kB signaling pathway of fibroblasts from uterine fibroids. Int J Clin Exp Pathol. 2015-11-30 [PMID: 26617709] (Func, Human)	Func	Human
Benbow JH, Thompson KJ, Cope HL et al. Diet-Induced Obesity Enhances Progression of Hepatocellular Carcinoma through Tenascin-C/Toll-Like Receptor 4 Signaling. Am. J. Pathol. 2015-11-18 [PMID: 26603137] (Mouse, Human) Details: TLR4 Inhibitor Peptide Set/VIPER was used for in vitro experiments on Huh 7.0 and Raw 264.7 cells - the cells were preincubated with either 25 uM VIPER or with the control peptide (CP7) 90 minutes before treatment with Tenascin-C and/or lipopolysaccharide.		Mouse, Human
Gomersall AC, Phan HA, Iacuone S et al. The Mycoplasma hyorhinis p37 Protein Rapidly Induces Genes in Fibroblasts Associated with Inflammation and Cancer. PLoS ONE. 2015-10-30 [PMID: 26512722] (Func, Mouse) Details: The Viral Inhibitor Peptide of Tlr4 /VIPER and the VIPER control peptide CP7 (TLR4 Inhibitor Peptide Set IMG-2011set) was used at working concentration of 0.5 uM on NIH3T3 cells for reducing the expression of p37-induced serum amyloid A3/Saa3 from 12-fold to 5-fold.	Func	Mouse
Sung DK, Chang YS, Sung SI et al. Antibacterial effect of mesenchymal stem cells against Escherichia coli is mediated by secretion of beta-defensin-2 via toll like receptor 4 signaling. Cell. Microbiol. 2015-09-09 [PMID: 26350435] (Func, In vitro, Human)	Func, In vitro	Human
Rannikko EH, Weber SS, Kahle PJ. Exogenous a-synuclein induces toll-like receptor 4 dependent inflammatory responses in astrocytes. BMC Neurosci 2015-09-08 [PMID: 26346361] (Func, In vitro, Mouse)	Func, In vitro	Mouse
Estruch M, Rajamaki K, Sanchez-Quesada JL et al. Electronegative LDL induces priming and inflammasome activation leading to IL-1b release in human monocytes and macrophages. Biochim. Biophys. Acta 2015-11-01 [PMID: 26327597] (Func, In vitro, Human)	Func, In vitro	Human
Uraki S, Tameda M, Sugimoto K et al. Substitution in Amino Acid 70 of Hepatitis C Virus Core Protein Changes the Adipokine Profile via Toll-Like Receptor 2/4 Signaling PLoS ONE. 2015-06-30 [PMID: 26121241] (Func)	Func
Jain S, Suklabaidya S, Das B et al. TLR4 activation by lipopolysaccharide confers survival advantage to growth factor deprived prostate cancer cells Prostate 2015-04-02 [PMID: 25833062] (Func, In-vitro, Human)	Func, In-vitro	Human
Masson GS, Nair AR, Dange RB et al. Toll-like receptor 4 promotes autonomic dysfunction, inflammation and microglia activation in the hypothalamic paraventricular nucleus: role of endoplasmic reticulum stress. PLoS One. 2015-05-26 [PMID: 25811788] (In-vivo, Rat)	In-vivo	Rat
Wang D, Gilbert JR, Shaw MA et al. Toll-like receptor 4 mediates the regenerative effects of bone grafts for calvarial bone repair Tissue Eng Part A. 2015-01-20 [PMID: 25603990] (In Vivo, Mouse) Details: TLR4 Inhibitor Peptide Set / VIPER TLR4 Inhibitor used for in-vivo inhibition of TLR4 in experiments involving regenerative effects of bone grafts for calvarial bone repair. VIPER was used at 0.3mg/ml concentration in fractionated bone components/morselized bone which was employed for treating calvarial defects in wildtype and global TLR4-/- knockout mouse strains.	In Vivo	Mouse
Gillenius E, Urban CF. et al. The adhesive protein invasin of Yersinia pseudotuberculosis induces neutrophil extracellular traps via beta1 integrins Microbes Infect. 2015-01-07 [PMID: 25576025] (B/N, Human) Details: TLR4 Inhibitor Peptide /TLR-4 antagonist peptide viper alongwith control peptide CP7 was used on human polymorphonuclear neutrophils that were harvested from the blood of healthy volunteers. Fig. 5. PMNs were pre-treated with 4 uM of TLR-4 peptide inhibitor Viper or control peptide/CP7 30 minutes prior to extracellular DNA quantification (extracellular DNA fluorescence assay) in response to infection with YPIII pIB1 /Yersinia pseudotuberculosis MOI 30, E. coli MOI 100. The data is shown in Fig 5D.	B/N	Human
Tun X, Yasukawa K, Yamada KI. Involvement of nitric oxide with activation of Toll-like receptor 4 signaling in mice with dextran sodium sulfate-induced colitis. Free Radic. Biol. Med. 2014-06-30 [PMID: 24992835] (In vitro, Mouse) Details: TLR4 Inhibitor Peptide VIPER used at 10 uM final concentration in ESR/spin trapping assay of NO produced in-vitro in mouse colon tissues (see protocol details in full text).	In vitro	Mouse
Shimizu T, Kimura Y, Kida Y et al. Cytadherence of Mycoplasma pneumoniae Induces Inflammatory Responses through Autophagy and Toll-like Receptor 4. Infect. Immun. 2014-05-05 [PMID: 24799628] (In vitro, B/N, Mouse) Details: Mouse peritoneal macrophages, Fig 4A. Cells were pretreated with 50 uM TLR4 inhibitor prior to M pneumoniae infection. Readout system: TNF-alpha ELISA. The results showed that the TLR4 inhibitor decreased M pneumoniae TNF-alpha induction.	In vitro, B/N	Mouse
Kumalasari ID, Nishi K, Putra AB, Sugahara T. Activation of macrophages stimulated by the bengkoang fiber extract through toll-like receptor 4. Food Funct. 2014-04-28 [PMID: 24770453] (B/N, In vitro, Mouse) Details: Mouse J774.1 macrophage-like cells, Fig 3A. The cells were treated with combinations 5 uM TLR4 inhibitor peptide (5 um) and bengkoang fiber extract (BFE, 27 mg/ml); BFE stimulates macrophage activation. Readout system: IL-6 and TNF-alpha ELISA assays. The	B/N, In vitro	Mouse
Estruch M, Sanchez-Quesada JL, Ordóñez-Llanos J, Benítez S. Ceramide-enriched LDL induces cytokine release through TLR4 and CD14 in monocytes. Similarities with electronegative LDL. Clin Investig Arterioscler 2014-03-11 [PMID: 24630524] (Func, In vitro, Human) Details: Primary monocytes, Fig 2A.	Func, In vitro	Human
Moriya R, Takahashi K, Kitahara A et al. Possible involvement of PI3K-dependent pathways in the increased VEGF120 release from osteoblastic cells preloaded with palmitate in vitro. Biochem. Biophys. Res. Commun. 2014-01-31 [PMID: 24491567] (Forced Spectroscopy, Rat) Details: Palmitate-stimulated rat UMR-106 osteosarcoma cells, Fig 2C	Forced Spectroscopy	Rat
Putra AB, Nishi K, Shiraishi R et al. Jellyfish collagen stimulates production of TNF-alpha and IL-6 by J774. 1 cells through activation of NF-kB and JNK via TLR4 signaling pathway. Mol Immunol 2013-11-26 [PMID: 24291243] (Func, Mouse)	Func	Mouse
Itoh T, Miyake Y, Onda A et al. Immunomodulatory effects of heat-killed Enterococcus faecalis TH10 on murine macrophage cells. Microbiologyopen. 2012-12-01 [PMID: 23233442]
Leow-Dyke S, Allen C, Denes A et al. Neuronal Toll-like receptor 4 signaling induces brain endothelial activation and neutrophil transmigration in vitro. J Neuroinflammation. 2012-10-03 [PMID: 23034047]
Ochi A, Nguyen AH, Bedrosian AS et al. MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells. J Exp Med. 2012-08-27 [PMID: 22908323]
Stack J, Bowie AG. Poxviral protein A46 antagonizes Toll-like receptor 4 signaling by targeting BB loop motifs in Toll-IL-1 receptor adaptor proteins to disrupt receptor:adaptor interactions. J Biol Chem. 2012-06-29 [PMID: 22593572]
Oda S, Franklin E, Khan AR. Poxvirus A46 protein binds to TIR domain-containing Mal/TIRAP via an a-helical sub-domain. Mol Immunol. 2011-09-01 [PMID: 21831443]
Show All 47 Publications. Collapse Publications.

Images	Ratings	Applications	Species	Date	Details
Enlarge	5 reviewed by: anonymous aa	ELISA	Human	09/15/2014	View Summary Application ELISA Sample Tested THP-1 cell culture supernatant Species Human

Array NBP2-26244

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