Recruitment of TLR adapter TRIF to TLR4 signaling complex is mediated by the second helical region of TRIF TIR domain
Open accessAbstract
Significance: This study sheds light on the mechanisms of Toll-like receptor 4 (TLR4) signaling complex assembly. Particularly, the interaction site that mediates Toll/IL-1R resistance (TIR) domain–containing adapter-inducing IFN-β (TRIF) recruitment to the TLR4 signaling complex is identified within the second helical region of the TRIF TIR domain. This finding is significant because “a mimic” of this site potently inhibits TLR4 signaling in cells by a competitive mechanism and decreases LPS-induced mortality in mice by more than 80%.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Determined serum IL-6 levels agree with previously reported values after PHx (1-2 ng/mL) and LPS treatment (175 ng/mL) of mice.
“Determined serum levels agree with previously reported values after PHx (1–2 ng/mL; Nechemia-Arbely et al., 2011; Yin et al., 2011) and LPS treatment (175 ng/mL; Piao et al., 2013) of mice.”
From Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib (2017) · cites this paper as Piao et al., 2013
The ‘TF5 Blunts LPS-Induced Cytokine Response’ section reports measuring circulating IL-6 after LPS treatment of mice, and the Fig. 4 caption specifies that the samples were plasma. Our copy does not state the cited value of 175 ng/mL or identify the samples as serum. The PHx values are attached to other citations, not Piao et al. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in <i>Tlr4</i> Gene
Poltorak, A., He, X., Smirnova, I., Liu, M.-Y., Huffel, C. V., Du, X., Birdwell, D., Alejos, E., Silva, M., Galanos, C., et al. (1998) · Science · doi:10.1126/science.282.5396.2085 · Cited by 7,631 · see citing works
How to measure and predict the molar absorption coefficient of a protein
Pace, C., Vajdos, F., Fee, L. R., Grimsley, G., & Gray, T. (1995) · Protein Science · doi:10.1002/pro.5560041120 · Cited by 3,924 · see citing works
Hoshino, K., Takeuchi, O., Kawai, T., Sanjo, H., Ogawa, T., Takeda, Y., Takeda, K., & Akira, S. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.7.3749 · Cited by 3,374 · see citing works
Unresponsiveness of MyD88-deficient mice to endotoxin.
Kawai, T., Adachi, O., Ogawa, T., Takeda, K., & Akira, S. (1999) · Immunity · doi:10.1016/s1074-7613(00)80086-2 · Cited by 2,367 · see citing works
Whitmore, L., & Wallace, B. A. (2007) · Biopolymers · doi:10.1002/bip.20853 · Cited by 2,247 · see citing works
The third helix of the Antennapedia homeodomain translocates through biological membranes.
Derossi, D., Joliot, A., Chassaing, G., & Prochiantz, A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34080-2 · Cited by 2,034 · see citing works
A family of human receptors structurally related to Drosophila Toll.
Rock, F., Hardiman, G., Timans, J., Kastelein, R., & Bazan, J. (1998) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.95.2.588 · Cited by 2,009 · see citing works
MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways.
Medzhitov, R., Preston-Hurlburt, P., Kopp, E., Stadlen, A., Chen, C.-Q., Ghosh, S., & Janeway, C. (1998) · Molecules and Cells · doi:10.1016/s1097-2765(00)80136-7 · Cited by 1,783 · see citing works
Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction
Fitzgerald, K. A., Pålsson‐McDermott, E. M., Bowie, A., Jefferies, C. A., Mansell, A. S., Brady, G., Brint, E. K., Dunne, A., Gray, P., Harte, M. T., et al. (2001) · Nature · doi:10.1038/35092578 · Cited by 1,258 · see citing works
TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β
Kagan, J. C., Su, T., Horng, T., Chow, A. Y., Akira, S., & Medzhitov, R. M. (2008) · Nature Immunology · doi:10.1038/ni1569 · Cited by 1,256 · see citing works
Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4
Pålsson‐McDermott, E. M., & O'Neill, L. A. J. (2004) · Immunology · doi:10.1111/j.1365-2567.2004.01976.x · Cited by 1,254 · see citing works
Yamamoto, M., Sato, S., Mori, K., Hoshino, K., Takeuchi, O., Takeda, K., & Akira, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.12.6668 · Cited by 1,227 · see citing works
Oshiumi, H., Matsumoto, M., Funami, K., Akazawa, T., & Seya, T. (2003) · Nature Immunology · doi:10.1038/ni886 · Cited by 1,208 · see citing works
LPS-TLR4 Signaling to IRF-3/7 and NF-κB Involves the Toll Adapters TRAM and TRIF
Fitzgerald, K. A., Rowe, D. C., Barnes, B. J., Caffrey, D. R., Visintin, A., Latz, E., Monks, B. G., Pitha, P. M., & Golenbock, D. T. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20031023 · Cited by 1,193 · see citing works
A Self-Consistent Method for the Analysis of Protein Secondary Structure from Circular Dichroism
Sreerama, N., & Woody, R. W. (1993) · Analytical Biochemistry · doi:10.1006/abio.1993.1079 · Cited by 1,056 · see citing works
Andrade, M. A., Chacón, P., Merelo, J. J., & Morán, F. (1993) · Protein Engineering Design and Selection · doi:10.1093/protein/6.4.383 · Cited by 1,007 · see citing works
Structural basis for signal transduction by the Toll/interleukin-1 receptor domains
Xu, Y., Tao, X., Shen, B., Horng, T., Medzhitov, R. M., Manley, J. L., & Tong, L. (2000) · Nature · doi:10.1038/35040600 · Cited by 815 · see citing works
The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors
Horng, T., Barton, G. M., Flavell, R. A., & Medzhitov, R. M. (2002) · Nature · doi:10.1038/nature01180 · Cited by 809 · see citing works
TLR4, but not TLR2, mediates IFN-β–induced STAT1α/β-dependent gene expression in macrophages
Toshchakov, V. Y., Jones, B. W., Perera, P., Thomas, K., Cody, M. J., Zhang, S., Williams, B. R. G., Major, J. A., Hamilton, T. A., Fenton, M. J., et al. (2002) · Nature Immunology · doi:10.1038/ni774 · Cited by 803 · see citing works
Self-citationOshiumi, H., Sasai, M., Shida, K., Fujita, T., Matsumoto, M., & Seya, T. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305820200 · Cited by 411 · see citing works
Slack, J. L., Schooley, K., Bonnert, T. P., Mitcham, J. L., Qwarnström, E. E., Sims, J. E., & Dower, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.7.4670 · Cited by 315 · see citing works
Björkbacka, H., Fitzgerald, K. A., Huet, F., Li, X., Gregory, J. A., Lee, M. A., Ordija, C. M., Dowley, N. E., Golenbock, D. T., & Freeman, M. W. (2004) · Physiological Genomics · doi:10.1152/physiolgenomics.00128.2004 · Cited by 289 · see citing works
Protein Physics: A Course of Lectures
Finkel‘štejn, A. V., & Pticyn, O. B. (2002) · Medical Entomology and Zoology · Cited by 247 · see citing works
Chemical, Physical, and Biological Properties of a Lipopolysaccharide from Escherichia coli K-235 *
McIntire, F. C., Sievert, H. W., Barlow, G. H., Finley, R. A., & Lee, A. Y. (1967) · Biochemistry · doi:10.1021/bi00860a011 · Cited by 247 · see citing works
Dunne, A., Ejdebäck, M., Ludidi, P. L., O'Neill, L., & Gay, N. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301742200 · Cited by 235 · see citing works
Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling
Ohnishi, H., Tochio, H., Kato, Z., Orii, K. E., Li, A., Kimura, T., Hiroaki, H., Kondo, N., & Shirakawa, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812956106 · Cited by 218 · see citing works
Nyman, T., Stenmark, P., Flodin, S., Johansson, I., Hammarström, M., & Nordlund, P. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.c800001200 · Cited by 193 · see citing works
Tryptophan fluorescence study of the interaction of penetratin peptides with model membranes
Christiaens, B., Symoens, S., Vanderheyden, S., Engelborghs, Y., Joliot, A., Prochiantz, A., Vandekerckhove, J. S., Rosseneu, M., & Vanloo, B. (2002) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2002.02963.x · Cited by 191 · see citing works
Miguel, R. N., Wong, J., Westoll, J. F., Brooks, H. J., O'Neill, L. A. J., Gay, N. J., Bryant, C. E., & Monie, T. P. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000788 · Cited by 189 · see citing works
Berlose, J., Convert, O., Derossi, D., Brunissen, A., & Chassaing, G. (1996) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1996.0372r.x · Cited by 163 · see citing works
Valkov, E., Stamp, A. L., DiMaio, F., Baker, D. A., Verstak, B., Roversi, P., Kellie, S., Sweet, M. J., Mansell, A. S., Gay, N. J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1104780108 · Cited by 138 · see citing works
Crystal Structure of the Toll/Interleukin-1 Receptor Domain of Human IL-1RAPL
Khan, J., Brint, E. K., O'Neill, L. A. J., & Tong, L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403434200 · Cited by 132 · see citing works
Lysakova-Devine, T., Keogh, B., Harrington, B., Nagpal, K., Halle, A., Golenbock, D. T., Monie, T. P., & Bowie, A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002013 · Cited by 131 · see citing works
Snyder, G. A., Cirl, C., Jiang, J., Chen, K., Waldhuber, A., Smith, P., Römmler, F., Snyder, N. W., Fresquez, T., Dürr, S., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215770110 · Cited by 91 · see citing works
Toshchakov, V. Y., Basu, S., Fenton, M. J., & Vogel, S. N. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.494 · Cited by 90 · see citing works
Self-citationToshchakov, V. Y., Fenton, M. J., & Vogel, S. N. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.5.2655 · Cited by 81 · see citing works
Self-citationStructural Insights into TIR Domain Specificity of the Bridging Adaptor Mal in TLR4 Signaling
Lin, Z., Lu, J., Zhou, W., & Shen, Y. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034202 · Cited by 81 · see citing works
Toshchakov, V. Y., Szmacinski, H., Couture, L. A., Lakowicz, J. R., & Vogel, S. N. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1002424 · Cited by 77 · see citing works
Self-citationCouture, L. A., Piao, W., Ru, L. W., Vogel, S. N., & Toshchakov, V. Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.360925 · Cited by 72 · see citing works
Self-citationCzajlik, A., Mesko, E., Penke, B., & Perczel, A. (2002) · Journal of Peptide Science · doi:10.1002/psc.380 · Cited by 51 · see citing works
Inhibition of TLR4 Signaling by TRAM-Derived Decoy Peptides In Vitro and In Vivo
Piao, W., Vogel, S. N., & Toshchakov, V. Y. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202703 · Cited by 48 · see citing works
Self-citationCell-penetrating TIR BB loop decoy peptides
Toshchakov, V. Y., & Vogel, S. N. (2007) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.7.7.1035 · Cited by 47 · see citing works
Self-citationStructure and regulation of cytoplasmic adapter proteins involved in innate immune signaling
Monie, T., Moncrieffe, M. C., & Gay, N. J. (2009) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00735.x · Cited by 36 · see citing works
Investigation of penetratin peptides
Czajlik, A., Mesko, E., Penke, B., & Andras, P. (2002) · Cited by 23 · see citing works
Flagged first, then by citations
1 of the 45 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Innate Immune Pattern Recognition: A Cell Biological Perspective
Brubaker, S. W., Bonham, K. S., Zanoni, I., & Kagan, J. C. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112240 · Cited by 1,475 · see citing works
Assembly and localization of Toll-like receptor signalling complexes
Gay, N. J., Symmons, M. F., Gangloff, M., & Bryant, C. E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3713 · Cited by 832 · see citing works
TLR4 Signaling Pathway Modulators as Potential Therapeutics in Inflammation and Sepsis
Kuzmich, N. N., Сивак, К. В., Chubarev, V. N., Porozov, Y. B., Savateeva-Lyubimova, T. N., & Peri, F. (2017) · Vaccines · doi:10.3390/vaccines5040034 · Cited by 640 · see citing works
“The same group also has designed and synthesized TRIF TIR domain-derived decoy peptides [164].”
BackgroundToll-like Receptors in the Vascular System: Sensing the Dangers Within
Goulopoulou, S., McCarthy, C. G., & Webb, R. C. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.010090 · Cited by 261 · see citing works
Below the surface: The inner lives of TLR4 and TLR9
Marongiu, L., Gornati, L., Artuso, I., Zanoni, I., & Granucci, F. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.3mir1218-483rr · Cited by 155 · see citing works
The roles of catechins in regulation of systemic inflammation
Kim, J. M., & Heo, H. J. (2022) · Food Science and Biotechnology · doi:10.1007/s10068-022-01069-0 · Cited by 124 · see citing works
“receptor (TIR) domain-containing adaptors, such as myeloid differentiation primary response 88 (MyD88), Toll/ interleukin-1 receptor domain-containing adapter protein (TIRAP), and TIR-domain-containing adapter-inducing interferon-b (TRIF) (Piao et al., 2013).”
BackgroundThe Architecture of the TIR Domain Signalosome in the Toll-like Receptor-4 Signaling Pathway
Guven‐Maiorov, E., Keskin, Ö., Gürsoy, A., Waes, C. V., Chen, Z., Tsai, C., & Nussinov, R. (2015) · Scientific Reports · doi:10.1038/srep13128 · Cited by 124 · see citing works
TLR4 has a TP53-dependent dual role in regulating breast cancer cell growth
Haricharan, S., & Brown, P. H. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1420811112 · Cited by 86 · see citing works
“(Right) In TP53 mutant cells, TLR4-mediated up-regulation of cell growth occurs through (1) TLR4 activation by ligands; (2) TLR4-mediated induction of proinflammatory cytokines, including CXCL1; (3) autocrine growth promotion by cytokine; and (4) TLR4-mediated inhibition of anti-growth cytokines, such as CD154.”
BackgroundInfluentialAhmad, R., Al-Roub, A., Kochumon, S., Akther, N., Thomas, R., Kumari, M., Koshy, M., Tiss, A., Hannun, Y. A., Tuomilehto, J., et al. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701552 · Cited by 84 · see citing works
From Obesity to Hippocampal Neurodegeneration: Pathogenesis and Non-Pharmacological Interventions
Lee, T. H.-Y., & Yau, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010201 · Cited by 76 · see citing works
Ko, R., Park, J. H., Ha, H., Choi, Y., & Lee, S. Y. (2015) · Nature Communications · doi:10.1038/ncomms7765 · Cited by 75 · see citing works
A Decoy Peptide that Disrupts TIRAP Recruitment to TLRs Is Protective in a Murine Model of Influenza
Piao, W., Shirey, K. A., Ru, L. W., Lai, W., Szmacinski, H., Snyder, G. A., Sundberg, E. J., Lakowicz, J. R., Vogel, S. N., & Toshchakov, V. Y. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.05.035 · Cited by 64 · see citing works
“…of TIR-containing proteins in a functional signaling complex, as well as the composition and stoichiometry of components in the immediate receptor complexes, is still debated ((Gay et al., 2014) for a recent review; (Piao et al., 2013a) and (Enokizono et al., 2013) for an example of debate).”
InfluentialSelf-citationSARM modulates MyD88-mediated TLR activation through BB-loop dependent TIR-TIR interactions
Carlsson, E., Ding, J. L., & Byrne, B. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2015.11.021 · Cited by 55 · see citing works
Toll-like receptor 4: An attractive therapeutic target for acute kidney injury
Jha, A. K., Gairola, S., Kundu, S., Doye, P., Syed, A. M., Ram, C., Murty, U. S., Naidu, V. G. M., & Sahu, B. D. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119155 · Cited by 52 · see citing works
Functional interfaces between TICAM-2/TRAM and TICAM-1/TRIF in TLR4 signaling
Funami, K., Matsumoto, M., Oshiumi, H., Inagaki, F., & Seya, T. (2017) · Biochemical Society Transactions · doi:10.1042/bst20160259 · Cited by 47 · see citing works
Pisoschi, A. M., Iordache, F., Stanca, L., Cimpeanu, C. L., Furnaris, F., Geicu, O. I., Bîlteanu, L., & Șerban, A. I. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.116075 · Cited by 48 · see citing works
A survey of TIR domain sequence and structure divergence
Toshchakov, V. Y., & Neuwald, A. F. (2020) · Immunogenetics · doi:10.1007/s00251-020-01157-7 · Cited by 46 · see citing works
Self-citationZhang, X., Jiang, D., & Li, H. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12881 · Cited by 44 · see citing works
“Similarly to TLR3, TLR4 can induce IFN gene expression in a MyD88-independent and TRIF- and TBK1-dependent pathway; however, this induction is limited to the gene encoding IFN-β and excludes IFN-α (Piao et al., 2013).”
BackgroundHasan, A., Akhter, N., Al-Roub, A., Thomas, R., Kochumon, S., Wilson, A., Koshy, M., Al‐Ozairi, E., Al‐Mulla, F., & Ahmad, R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20174112 · Cited by 44 · see citing works
“These findings are in line with previous work demonstrating that blockade of TLR4/TRIF complex formation inhibits LPS-induced cytokine production [68].”
ResultPiao, W., Xiong, Y., Famulski, K. S., Brinkman, C. C., Li, L., Toney, N., Wagner, C., Saxena, V., Simon, T., & Bromberg, J. S. (2018) · Nature Communications · doi:10.1038/s41467-018-05412-0 · Cited by 44 · see citing works
Self-citationJin, F., Li, J., Guo, J., Doeppner, T. R., Hermann, D. M., Yao, G., & Dai, Y. (2021) · European Heart Journal Open · doi:10.1093/ehjopen/oeab022 · Cited by 41 · see citing works
“However, the pro-inflammatory IFN b -STAT1 axis, 86 but not IRF3 known to directly control transcription of IFNB1 (interferon beta 1), is impaired in HADC3 - / - macrophages exposed to LPS.”
BackgroundThe roles played by TLR4 in the pathogenesis of multiple sclerosis; A systematic review article
Manjili, F. A., Yousefi‐Ahmadipour, A., & Arababadi, M. K. (2020) · Immunology Letters · doi:10.1016/j.imlet.2020.02.004 · Cited by 34 · see citing works
Liao, Y., Kong, Y., Chen, H., Xia, J., Zhao, J., & Zhou, Y. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113821 · Cited by 34 · see citing works
Li, Y., Xiong, Y., Wang, Z., Han, J., Shi, S., He, J., Shen, N., Wu, W., Wang, R., Lv, W., et al. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02244-9 · Cited by 31 · see citing works
Sobotta, S., Raue, A., Huang, X., Vanlier, J., Jünger, A., Bohl, S., Albrecht, U., Hahnel, M. J., Wolf, S., Mueller, N. S., et al. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00775 · Cited by 28 · see citing works
“, 2011) and inflammation (Waage et al., 1989; Damas et al., 1992; Piao et al., 2013), but a direct comparison of regenerative and inflammatory conditions has not been performed yet.”
BackgroundAwasthi, S., Singh, B., Ramani, V., Xie, J., & Kosanke, S. D. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210979 · Cited by 28 · see citing works
Differential adapter recruitment by TLR2 co-receptors
Piao, W., Ru, L. W., & Toshchakov, V. Y. (2016) · Pathogens and Disease · doi:10.1093/femspd/ftw043 · Cited by 26 · see citing works
“In this approach, tagged TIR domains are expressed in cells and then immunoprecipitated from cell lysates supplemented with decoy peptides (Piao et al. 2013, 2015).”
BackgroundMethodInfluentialSelf-citationFeng, W., Gu, Y., Nie, L., Guo, D., Xiang, L., & Shao, J.-Z. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502334 · Cited by 26 · see citing works
Rethinking Toll-like receptor signalling
Bryant, C. E. (2024) · Current Opinion in Immunology · doi:10.1016/j.coi.2024.102460 · Cited by 23 · see citing works
Achek, A., Kwon, H., Patra, M. C., Shah, M., Hong, R., Lee, W., Baek, W., Choi, Y. S., Kim, G., Pham, T. L. H., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102645 · Cited by 23 · see citing works
“Additionally, the surface exposed TIR peptides from TRIF, TRAM, and TIRAP have been explored to obtain effective TLR inhibitors [28,30,61].”
BackgroundToshchakov, V. Y., & Javmen, A. (2020) · Innate Immunity · doi:10.1177/1753425919844310 · Cited by 18 · see citing works
Self-citationBlocking TIR Domain Interactions in TLR9 Signaling
Javmen, A., Szmacinski, H., Lakowicz, J. R., & Toshchakov, V. Y. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800194 · Cited by 18 · see citing works
Self-citationEnderes, J., Mallesh, S., Schneider, R., Hupa, K. J., Lysson, M., Schneiker, B., Händler, K., Schlotmann, B. C., Günther, P. S., Schultze, J. L., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.581111 · Cited by 16 · see citing works
“A counterbalance of the MyD88 pathway toward the TRIF pathway or intrinsic inhibitory effects of TRIF as described for TF5 - a TRIF-derived peptide - that inhibits TLR4 in a mouse model of LPS-induced inflammation (35) might be a possible explanation for this observation.”
ResultMahita, J., & Sowdhamini, R. (2017) · Biology Direct · doi:10.1186/s13062-017-0179-0 · Cited by 16 · see citing works
“Fitzgerald KA, Rowe DC, Barnes BJ, Caffrey DR, Visintin A, Latz E, et al. LPSTLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF.”
BackgroundInfluentialHuman MD2 deficiency—an inborn error of immunity with pleiotropic features
Li, Y., Yu, Z., Schenk, M., Lagovsky, I., Illig, D., Walz, C., Rohlfs, M., Conca, R., Muise, A. M., Snapper, S. B., et al. (2022) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2022.09.033 · Cited by 15 · see citing works
Allette, Y. M., Kim, Y.-S., Randolph, A. L., Smith, J. A., Ripsch, M. S., & White, F. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-03447-9 · Cited by 15 · see citing works
Inhibition of TLR4 signaling by Brucella TIR-containing protein TcpB-derived decoy peptides
Ke, Y., Li, W., Wang, Y., Yang, M., Guo, J., Zhan, S., Du, X., Wang, Z., Yang, M., Li, J., et al. (2016) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2016.05.003 · Cited by 14 · see citing works
Huang, W., Yang, J. M., He, C., & Yang, J. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.11242 · Cited by 14 · see citing works
Khodabandehloo, F., Aflatoonian, R., Zandieh, Z., Rajaei, F., Sayahpour, F., Nassiri‐Asl, M., & Eslaminejad, M. B. (2021) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.16506 · Cited by 13 · see citing works
Wu, M., Liu, F., Li, Y., Huang, R., Hu, R., Zhu, J. S., Li, S., & Long, C. (2022) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770.2022.2057535 · Cited by 12 · see citing works
“[16] TLRs can activate mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-kB) to produce proinflammatory cytokines.[17] Toll-like receptor 4 (TLR4), a member of TLRs, has been reported to widely participate in OA development.”
Fazio, L. L., Billod, J., Lorenzo, F. D., Paciello, I., Pallach, M., Francisco, S., Holgado, A., Beyaert, R., Fresno, M., Shimoyama, A., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01888 · Cited by 12 · see citing works
“org August 2018 | Volume 9 | Article 1888 proteins Mal (also called TIRAP), TRIF, and TRAM, allowing the expression of genes encoding type 1 interferon and interferonassociated genes (40, 41).”
BackgroundMavrommatis, A., Θεοδώρου, Γ., Politis, I., & Tsiplakou, E. (2021) · Cytokine · doi:10.1016/j.cyto.2021.155588 · Cited by 11 · see citing works
Does hypometabolism constrain innate immune defense?
Kadamani, K. L., Logan, S. M., & Pamenter, M. E. (2024) · Acta Physiologica · doi:10.1111/apha.14091 · Cited by 7 · see citing works
“61,87 For example, NF-κ B upregulates Hifa expression in macrophages and the hypoxia-induced increase of HIF-1 α within the nucleus involves NF-κ B-mediated transcriptional control.”
BackgroundABCA1 plays an anti-inflammatory role by affecting TLR4 at the feto–maternal interface
Ding, N., Liu, N., Yang, L., Han, X., Lin, L., & Long, Y. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118390 · Cited by 7 · see citing works
Wu, B., Xu, Z., Cao, J., Wang, Q., Mei, J., & Xie, J. (2022) · Aquaculture and Fisheries · doi:10.1016/j.aaf.2022.03.001 · Cited by 7 · see citing works
Frontline Science: Targeting the TLR7 signalosome assembly
Javmen, A., Szmacinski, H., Lakowicz, J. R., & Toshchakov, V. Y. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.2hi0819-180r · Cited by 5 · see citing works
Self-citationAnin silicoapproach towards the identification of novel inhibitors of the TLR-4 signaling pathway
Mahita, J., Harini, K., Pichika, M. R., & Sowdhamini, R. (2015) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2015.1079243 · Cited by 5 · see citing works
“This observation is supported by previous findings in which two decoy peptides mimicking the BB loop and the αC helix-CD loop region of TRAM TIR were found to be inhibitory in vitro (Piao et al., 2013).”
ResultChandrasekaran, P., Uddandrao, V. V. S., Vadivukkarasi, S., Prabhu, P., & Ganapathy, S. (2024) · Indian Journal of Pharmaceutical Education and Research · doi:10.5530/ijper.58.2.60 · Cited by 4 · see citing works
Nandi, B. R., Patra, B., & Radhakrishnan, G. (2025) · Journal of Inflammation Research · doi:10.2147/jir.s526902 · Cited by 2 · see citing works
Lei, H., Wang, S., Guo, J., Yin, X., Yu, Q., Yang, M., Wang, Y., Ke, Y., & Li, W. (2019) · Molecular Biology Reports · doi:10.1007/s11033-019-04627-8 · Cited by 2 · see citing works
Peptide-Based Inhibitors of the Induced Signaling Protein Interactions: Current State and Prospects
Toshchakov, V. Y. (2024) · Biochemistry (Moscow) · doi:10.1134/s000629792405002x · Cited by 2 · see citing works
“In addition to the previously identified peptides derived from the BB loop of both adapter proteins [73], the inhibitory activity was observed for the peptide TM6 from the third helix in TRAM and peptide TF5 from the second helix in TRIF [55, 81].”
InfluentialSelf-citationZerrad, C., Lkhider, M., Belkouchi, A., Tanouti, I., Badre, W., Tahiri, M., Ayassi, S., Marchio, A., Pineau, P., Benjelloun, S., et al. (2023) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1080/15257770.2023.2225560 · Cited by 1 · see citing works
de Freitas, L. G. (2016) · doi:10.35376/10324/18651
“IRF3 e IRF7 promueven la producción de interferones tipo I (IFNA1 e IFN-β), importantes para las respuestas inmunitarias innatas antivíricas (ver figura 3 y 5) (20), (9), (21).”
BackgroundPierro, A. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732009889.793555356
The Protective Mechanism Against COVID-19, Antibody vs Cellular Immunity: An Extensive Review
Shrwani, K. J., Dhayhi, N., Mahallawi, W. H., Sherwani, A., Badedi, M., Aldossari, S. M., Muhajir, A., Hassan, Z., Sherwani, N., Karar, T., et al. (2023) · International Journal of Innovative Research in Medical Science · doi:10.23958/ijirms/vol08-i08/1721
Toshchakov, V. Y. (2024) · Biochemistry (Moscow) · doi:10.31857/s0320972524050025
Self-citationA systems biology investigation to identify potential biomarkers in leprosy-affected host cellsPreprint
Chowdhury, S., Ansari, A. I., Verma, P., Mavlankar, A., Tripathi, A., Peña, M. T., Sharma, R., Caskey, J., Truman, R. W., & Singh, P. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.03.28.646010
“The MYD88 independent pathway is also active by TLR4 where the receptor binds with TRAM:TRIF and goes on physically interacting with TAK1 [110,111].”
Toll-Like Receptors, PAMPs, and DAMPs in Hepatotoxicity
Zhang, Y., Kim, S. J., Zhang, H., & Tsung, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00270-9
Bonhomme, D. (2022) · theses.fr (ABES) · doi:10.70675/7e306522zb260z47f1za231zdb8fb8c2d9d5
- Authors
- Piao, W., Ru, L. W., Piepenbrink, K. H., Sundberg, E. J., Vogel, S. N., & Toshchakov, V. Y.
- Affiliations
- University of Maryland, Baltimore (US)
- Departments of aMicrobiology and Immunology,
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-11-05
- Volume
- 110
- Issue
- 47
- Pages
- 19036-19041
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3839745
- OpenAlex
- W2141941378
- Cited by
- 60
- References
- 45
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 8 · 2014: 2
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lincoln (University of Nebraska) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (AI082299)
- National Institute of Allergy and Infectious Diseases (R56AI018797, AI-095150, R01AI082299, AI018797, R37AI018797, AI082299, R01AI018797, R21AI095150)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- TRIF, TLR4, TIR domain, tram, TLR4 signaling, MyD88-independent signaling, type I interferon, NF-κB, sepsis, lipopolysaccharide-induced inflammation, macrophage activation
- MeSH terms
- Animals, Circular Dichroism, Escherichia coli, Mice, Inbred C57BL, Immunoblotting, Signal Transduction, Mutagenesis, Site-Directed, Interferon-beta, Receptors, Interleukin, Adaptor Proteins, Vesicular Transport, Immunoprecipitation, Toll-Like Receptor 4, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
