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Statins Decrease Toll-Like Receptor 4 Expression and Downstream Signaling in Human CD14 + Monocytes
Open accessAbstract
Objective— Anti-inflammatory effects of statins contribute to their clinical benefit. Molecular mechanisms underlying these effects have not been well explored. Because statins attenuate lipopolysaccharide (LPS) responsiveness, we hypothesized that part of the pleiotropic effects are mediated through innate immunity. Methods and Results— Toll-like receptor (TLR) 4 expression and downstream signaling in CD14 + monocytes after incubation with simvastatin and atorvastatin were quantified via flow-cytometry, quantitative RT-PCR, kinase assay, and enzyme-linked immunosorbent assay. Incubation with intermediates/ inhibitors of the mevalonate pathway was used to identify the mode of statin action. Statin incubation resulted in a dose-dependent reduction of TLR4 expression (53±7.6% reduction compared with untreated monocytes; P <0.005), transcript levels (68±6.3%; P <0.002), decreased IRAK phosphorylation (37±8.3%; P <0.05), and LPS-induced IL-6, IL-12, tumor necrosis factor (TNF)-α, and B7-1 expression ( P <0.05). Four weeks of treatment with atorvastatin significantly reduced TLR4 expression on circulating CD14 + monocytes by 36.2±4.2% ( P <0.05). Effects of statins were reversed by mevalonate ( P =0.57). Incubation with specific inhibitors of geranylgeranyltransferase (54±4.3%), farnesyltransferase (57±5.1%), or with clostridium-difficile toxin B (58±6.1%, P <0.01) imitated the statin effects. Whereas wortmannin and LY294002 inhibited the statin effect ( P =0.27), incubation with a specific RhoA kinase inhibitor had no effect ( P =0.57). Conclusions— Statins influence TLR4 expression and signaling via inhibition of protein geranylgeranylation and farnesylation. These observations imply interactions with innate immunity as one pleiotropic mechanism.
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“A similar effect was also observed in human CD14+ monocytes treated with atorvastatin, whereby TLR 4 expression was significantly down-regulated (Methe et al., 2005).”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Methe et al., 2005
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Cites
Akira, S., & Takeda, K. (2004) · Nature reviews. Immunology · doi:10.1038/nri1391 · Cited by 8,312
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 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
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
Medzhitov, R., Preston-Hurlburt, P., & Janeway, C. A. J. (1997) · Nature · doi:10.1038/41131 · Cited by 6,137
Toll-like receptors control activation of adaptive immune responses
Schnare, M., Barton, G. M., Czopik, A. K., Takeda, K., Akira, S., & Medzhitov, R. M. (2001) · Nature Immunology · doi:10.1038/ni712 · Cited by 1,364
Pleiotropic Effects of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors
Takemoto, M., & Liao, J. K. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/hq1101.098486 · Cited by 1,274
Zarember, K. A., & Godowski, P. J. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.168.2.554 · Cited by 1,251
Edfeldt, K., Swedenborg, J., Hansson, G. K., & Yan, Z.-Q. (2002) · PubMed · Cited by 847
Expression of Toll-Like Receptors in Human Atherosclerotic Lesions
Edfeldt, K., Swedenborg, J., Hansson, G. K., & Yan, Z.-Q. (2002) · Circulation · doi:10.1161/circ.105.10.1158 · Cited by 706
Abreu, M. T., Vora, P., Faure, E., Thomas, L. S., Arnold, E. T., & Arditi, M. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.3.1609 · Cited by 681
Xu, X.-O. H., Shah, P. K., Faure, E., Equils, O., Thomas, L. S., Fishbein, M. C., Luthringer, D., Xu, X., Rajavashisth, T. B., Yano, J., et al. (2001) · Circulation · doi:10.1161/hc5001.100631 · Cited by 676
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Li, C., Ma, M., Dong, S., Hong, Y., Bao, J., Zhang, Y., Gao, L., Cui, C., Guo, J., & He, L. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.635079 · Cited by 5
Ruleva, N. Y., Radyukhina, N. V., Zubkova, E., Filatova, A. Y., & Арефьева, Т. И. (2020) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-020-05042-x · Cited by 5
Bagheri, B., Sohrabi, B., Movassaghpur, A., Mashayekhi, S. O., Garjani, A., Shokri, M., Noori, M., & Garjani, A. (2013) · Advances in Bioscience and Biotechnology · doi:10.4236/abb.2013.47a1004 · Cited by 5
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Kumar, V. (2012) · InTech eBooks · doi:10.5772/25590 · Cited by 4
Arya, P., Nabi, S., & Bhandari, U. (2021) · PubMed Central · doi:10.22038/ijbms.2021.55460.12409 · Cited by 4
Sharifi, L., Moshiri, M., Dallal, M. M. S., Asgardoon, M. H., Nourizadeh, M., Bokaie, S., & Mirshafiey, A. (2018) · Recent Patents on Inflammation & Allergy Drug Discovery · doi:10.2174/1872213x13666181211160238 · Cited by 3
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Simone, M. D., Corsale, A. M., Presti, E. L., Scichilone, N., Picone, C., Giannitrapani, L., Dieli, F., & Meraviglia, S. (2022) · Cells · doi:10.3390/cells11213449 · Cited by 3
Wu, J., Yu, P., Hu, Z., & Zheng, S. (2007) · Medical Hypotheses · doi:10.1016/j.mehy.2007.06.008 · Cited by 2
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Reiss, C. S. (2016) · Springer eBooks · doi:10.1007/978-3-319-33189-8_8 · Cited by 3
Zeidan, N. (2013) · British Journal of Medicine and Medical Research · doi:10.9734/bjmmr/2013/3338 · Cited by 1
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Bai, L., Wang, Y., Qian, L., & Cui, J. (2021) · World Journal of Clinical Cases · doi:10.12998/wjcc.v9.i34.10392 · Cited by 1
Alshalmani, S. (2011) · Nottingham ePrints (University of Nottingham) · Cited by 1
Cell Signaling Pathways of the Innate Immune System During Acute Inflammation
Opal, S. M., & Cristofaro, P. A. (2006) · Springer eBooks · doi:10.1007/3-540-30328-6_3
Jaipersad, A. S. (2014) · University of Birmingham Institutional Research Archive (University of Birmingham)
Studies of immunoglobulin receptors and human proximal tubular cells
Natto, M. J. (2008) · Enlighten: Theses (The University of Glasgow)
Sánchez, J. P. (2011) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
WATERER, G. W. (2007) · Springer eBooks · doi:10.1007/978-3-540-34406-3_16
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Furuya, D. T. (2008) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2008.tde-16032009-125905
Ghavimi, H., & Hassanzadeh, K. (2015)
Azor, M. H. (2010) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2010.tde-02092010-182156
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Reiss, C. S. (2008) · Cambridge University Press eBooks · doi:10.1017/cbo9780511541728.018
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Hogg, J. C. (2011)
Innate immunity in viral encephalitis
Reiss, C. S. (2008) · Cambridge University Press eBooks · doi:10.1017/cbo9780511541728.019
ShaoPing, L., Zhang, Z., & LuAiqun, Q. (2014)
Zaidi, N., & Opal, S. M. (2009) · Elsevier eBooks · doi:10.1016/b978-1-4160-4252-5.50155-6
Taeb, M., Rahmani, M., Sharifi, L., & Mirshafiey, A. (2024) · British journal of healthcare and medical research · doi:10.14738/bjhmr.106.14305
Wasiak, S., Dzobo, K. E., Rakai, B. D., Kaiser, Y., Versloot, M., Bahjat, M., Stotz, S. C., Fu, L., Sweeney, M., Johansson, J. O., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13219203
Wasiak, S., Dzobo, K. E., Rakai, B. D., Kaiser, Y., Versloot, M., Bahjat, M., Stotz, S. C., Fu, L., Sweeney, M., Johansson, J. O., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13219206
Dormoi, J. (2013) · doi:10.70675/13e18b21z6d6ez48a8zb572z334611b8fa80
Varin, A. (2014) · theses.fr (ABES) · doi:10.70675/d46652b0z7942z481azab82z950d6f8312f8
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Metadata
- Authors
- Methe, H., Kim, J.-O., Kofler, S., Nabauer, M., & Weis, M.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- From the Department of Cardiology, Ludwig-Maximilians-University, Munich, Germany.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2005-07
- Volume
- 25
- Issue
- 7
- Pages
- 1439-1445
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2143835519
- Cited by
- 172
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 8 · 2020: 8 · 2019: 1 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 11 · 2014: 10 · 2013: 11 · 2012: 18
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- statins, simvastatin, atorvastatin, TLR4, CD14+ monocytes, innate immunity, lipopolysaccharide, mevalonate pathway, geranylgeranylation, farnesylation, geranylgeranyltransferase inhibitors, farnesyltransferase inhibitors, Clostridium difficile toxin B, anti-inflammatory activity, cytokine expression
- MeSH terms
- Atorvastatin, Phosphoinositide-3 Kinase Inhibitors, Adult, Bacterial Proteins, Bacterial Toxins, Cells, Cultured, Drug Interactions, Female, Heptanoic Acids, Humans, Lipopolysaccharides, Male, Middle Aged, Monocytes, Protein Kinases, Pyrroles, RNA, Messenger, Signal Transduction, Gene Expression, Cytokines, Protein Prenylation, B7-1 Antigen, Lipopolysaccharide Receptors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Phosphatidylinositol 3-Kinases, Protein Kinase Inhibitors, Toll-Like Receptor 4, Interleukin-1 Receptor-Associated Kinases
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