Inhibition of lipopolysaccharide‐induced cyclooxygenase‐2, tumor necrosis factor‐α and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195

Choi, Hyan B.; Khoo, C.; Ryu, Jae K.; Van Breemen, Edo; Kim, Seung U.; McLarnon, James G.

doi:10.1046/j.1471-4159.2002.01122.x

Cited by 83Neuroinflammation and Neurodegeneration MechanismsPharmacological Receptor Mechanisms and EffectsPain Mechanisms and Treatments

Inhibition of lipopolysaccharide‐induced cyclooxygenase‐2, tumor necrosis factor‐α and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195

Choi, Hyan B., Khoo, C., Ryu, Jae K., Van Breemen, Edo, Kim, Seung U., McLarnon, James G.·2002·Journal of Neurochemistry

DOI 10.1046/j.1471-4159.2002.01122.x

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Abstract

The anti-inflammatory actions of the mitochondrial peripheral benzodiazepine receptor (PBR) agonist PK11195 [1-(2-chloro- phenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide] were investigated in human microglia. Application of the microglial inflammatory stimulus lipopolysaccharide (LPS, at 100 ng/mL for 3 h), induced enhancement of the expressions of the inducible enzyme, cyclooxygenase-2 (COX-2) and the pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). PK11195 (at 50 microm) significantly inhibited the LPS-induced up-regulation of both inflammatory factors; at a lower concentration of PK11195 (2 microm) expression of TNF-alpha, but not COX-2, was reduced. Production of both factors, using immunocytochemistry for COX-2 and ELISA for TNF-alpha, was markedly reduced with 50 microm of PK11195 added to LPS solution. Acute application of LPS induced a transient increase in intracellular Ca2+[Ca2+]i exhibiting both a slow development and recovery in kinetic behavior. This increase in [Ca2+]i consisted primarily of a Ca2+ influx component accompanied by a smaller mobilization from intracellular Ca2+ stores. In the presence of PK11195, the amplitude of the [Ca2+]i response induced by LPS was reduced by 54%. Another mitochondrial agent cyclosporin A (CsA), which also acts at the permeability transition pore (PTP) of mitochondrial membrane but at a site different from the PBR, was ineffective in reducing either the LPS-induced expression of COX-2 and TNF-…

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In the CNS, TSPO is thought to be expressed by activated microglia.
“In the CNS, TSPO is thought to be expressed by activated microglia and, in addition, administration of the TSPO ligands in vivo or in vitro results in suppression of microglialactivation including inhibition of cytokine expression [12;13].”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [12]
TSPO ligands have anti-inflammatory properties, suggesting a role for TSPO in neuroinflammation.
“Additionally, since TSPO ligands have anti-inflammatory properties, suggesting a role for TSPO in neuroinflammation [12;13;22], an understanding of its cell type expression in various disease states may be a key resource in how to target the TSPO in these diseases.”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [12]
Administration of TSPO ligands in vivo or in vitro suppresses microglial activation, including inhibition of cytokine expression.
“In the CNS, TSPO is thought to be expressed by activated microglia and, in addition, administration of the TSPO ligands in vivo or in vitro results in suppression of microglialactivation including inhibition of cytokine expression [12;13].”
From Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain (2009) · cites this paper as [12]

Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes
Liu, J., Farmer, J. D., Lane, W. S., Friedman, J., Weissman, I., & Schreiber, S. L. (1991) · Cell · doi:10.1016/0092-8674(91)90124-h · Cited by 4,116 · see citing works
The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases
MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · see citing works
Calcineurin phosphatase activity in T lymphocytes is inhibited by FK 506 and cyclosporin A.
Fruman, D. A., Klee, C. B., Bierer, B. E., & Burakoff, S. J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.9.3686 · Cited by 823 · see citing works
SK&F 96365, a novel inhibitor of receptor-mediated calcium entry
Merritt, J. E., Armstrong, W. P., Benham, C. D., Hallam, T. J., Jacob, R., Jaxa‐Chamiec, A. A., Leigh, B. K., McCarthy, S., Moores, K., & RINK, T. J. (1990) · Biochemical Journal · doi:10.1042/bj2710515 · Cited by 768 · see citing works
Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart
Halestrap, A. P., Kerr, P. M., Javadov, S. A., & Woodfield, K. (1998) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(98)00122-4 · Cited by 485 · see citing works
Interactions of Cyclophilin with the Mitochondrial Inner Membrane and Regulation of the Permeability Transition Pore, a Cyclosporin A-sensitive Channel
Nicolli, A., Basso, E., Petronilli, V., Wenger, R. M., & Bernardi, P. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.4.2185 · Cited by 482 · see citing works
PK (‘peripheral benzodiazepine’) – binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK 11195 binding to activated microglia
Banati, R. B., Myers, R., & Kreutzberg, G. W. (1997) · Journal of Neurocytology · doi:10.1023/a:1018567510105 · Cited by 296 · see citing works
PK11195, a Ligand of the Mitochondrial Benzodiazepine Receptor, Facilitates the Induction of Apoptosis and Reverses Bcl-2-Mediated Cytoprotection
Hirsch, T., Decaudin, D., Susín, S. A., Marchetti, P., Larochette, N., Resche-Rigon, M., & Kroemer, G. (1998) · Experimental Cell Research · doi:10.1006/excr.1998.4084 · Cited by 254 · see citing works
Mitochondrial benzodiazepine receptor linked to inner membrane ion channels by nanomolar actions of ligands.
Kinnally, K. W., Zorov, D. B., Antonenko, Y. N., Snyder, S. H., McEnery, M. W., & Tedeschi, H. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.4.1374 · Cited by 205 · see citing works
Ion channels in microglia (brain macrophages)
Eder, C. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.275.2.c327 · Cited by 196 · see citing works
Generation and Characterization of Immortalized Human Microglial Cell Lines: Expression of Cytokines and Chemokines
Nagai, A., Nakagawa, E., Hatori, K., Choi, H. B., McLarnon, J. G., Lee, M. A., & Kim, S. U. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0437 · Cited by 153 · see citing works
Self-citation
PERIPHERAL ADMINISTRATION OF LIPOPOLYSACCHARIDE INDUCES ACTIVATION OF MICROGLIAL CELLS IN RAT BRAIN**This is one of eight original manuscripts on the subject “microglia”. Dr Peter Gebicke-Haerter (Dept. Psychiatry, University of Freiburg, Germany) acted as organiser and executive editor in the refereeing of these articles.
Buttini, M., Limonta, S., & Boddeke, H. W. G. M. (1996) · Neurochemistry International · doi:10.1016/0197-0186(95)00141-7 · Cited by 144 · see citing works
Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells
Canat, X., Carayon, P., Bouaboula, M., Cahard, D., Shire, D. J., Roque, C., Fur, G. L., & Casellas, P. (1993) · Life Sciences · doi:10.1016/0024-3205(93)90293-c · Cited by 144 · see citing works
T-cell costimulatory molecules B7-1 (CD80) and B7-2 (CD86) are expressed in human microglia but not in astrocytes in culture
Satoh, J., Lee, Y. B., & Kim, S. U. (1995) · Brain Research · doi:10.1016/0006-8993(95)01177-3 · Cited by 143 · see citing works
Self-citation
In vivo treatment with benzodiazepines inhibits murine phagocyte oxidative metabolism and production of interleukin 1, tumor necrosis factor and interleukin-6.
Zavala, F., Taupin, V., & Descamps‐Latscha, B. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22922-6 · Cited by 133 · see citing works
Role of mitochondrial Ca2+ regulation in neuronal and glial cell signalling1Published on the World Wide Web on December 3rd 1997.1
Simpson, P. B., & Russell, J. T. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(97)00056-8 · Cited by 113 · see citing works
Long-term activation of capacitative Ca2+ entry in mouse microglial cells
Toescu, E. C., Möller, T., Kettenmann, H., & Verkhratsky, A. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00123-7 · Cited by 103 · see citing works
Bacterial endotoxin induces [Ca2+]i transients and changes the organization of actin in microglia
Bader, M. F., Taupenot, L., Ulrich, G., Aunis, D., & Ciesielski-Treska, J. (1994) · Glia · doi:10.1002/glia.440110406 · Cited by 69 · see citing works
HSP72 induction by heat stress in human neurons and glial cells in culture
Satoh, J.-I., & Kim, S. U. (1994) · Brain Research · doi:10.1016/0006-8993(94)90396-4 · Cited by 63 · see citing works
Self-citation
Granulocyte macrophage colony stimulating factor stimulates in vitro proliferation of astrocytes derived from simian mature brains
Guillemin, G. J., Boussin, F. D., Grand, R. L., Croitoru‐Lamoury, J., Coffigny, H., & Dormont, D. (1996) · Glia · doi:10.1002/(sici)1098-1136(199601)16:1 · Cited by 62 · see citing works
Activation of purinergic P2X receptors inhibits P2Y-mediated Ca2+ influx in human microglia
Wang, X., Kim, S. U., van Breemen, C., & McLarnon, J. G. (2000) · Cell Calcium · doi:10.1054/ceca.2000.0110 · Cited by 51 · see citing works
Self-citation
Acute actions of tumor necrosis factor-α on intracellular Ca2+ and K+ currents in human microglia
McLarnon, J. G., Franciosi, S., Wang, X., Bae, J.-H., Choi, H. B., & Kim, S. U. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00119-1 · Cited by 45 · see citing works
Self-citation
Benzodiazepine anethesia in humans modulates the interleukin-1β, tumor necrosis factor-α and interleukin-6 responses of blood monocytes
Taupin, V., Jayais, P., Descamps‐Latscha, B., Cazalaà, J.-B., BARRIER, G., Bach, J., & Zavala, F. (1991) · Journal of Neuroimmunology · doi:10.1016/0165-5728(91)90157-3 · Cited by 41 · see citing works
Potential role of peripheral benzodiazepine receptors in inflammatory responses
Torres, S. R., Nardi, G. M., Ferrara, P., Ribeiro‐do‐Valle, R. M., & Farges, R. C. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00745-1 · Cited by 39 · see citing works
Inhibition of store‐operated Ca2+ influx by acidic extracellular pH in cultured human microglia
Khoo, C., Helm, J., Choi, H. B., Kim, S. U., & McLarnon, J. G. (2001) · Glia · doi:10.1002/glia.1092 · Cited by 32 · see citing works
Self-citation
Anion channels modulate store-operated calcium influx in human microglia
McLarnon, J. G., Helm, J., Goghari, V., Franciosi, S., Choi, H. B., Nagai, A., & Kim, S. U. (2000) · Cell Calcium · doi:10.1054/ceca.2000.0150 · Cited by 22 · see citing works
Self-citation
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Klegeris, A., McGeer, E. G., & McGeer, P. L. (2000) · Biochemical Pharmacology · doi:10.1016/s0006-2952(00)00252-5 · Cited by 21 · see citing works
Inflammatory Mechanisms of Alzheimer’s Disease
Rogers, J., & Griffin, W. S. T. (1998) · Humana Press eBooks · doi:10.1007/978-1-59259-473-3_6 · Cited by 14 · see citing works
Untitled work
(1997) · doi:10.1002/(sici)1097-4547(19971015)50:2

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Lee, M., Cho, T., Jantaratnotai, N., Wang, Y. T., McGeer, E. G., & McGeer, P. L. (2010) · The FASEB Journal · doi:10.1096/fj.09-149997 · Cited by 239 · see citing works
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Banati, R. B., Middleton, R. J., Chan, R., Hatty, C. R., Wai-Ying Kam, W., Quin, C., Graeber, M. B., Parmar, A., Zahra, D., Callaghan, P., et al. (2014) · Nature Communications · doi:10.1038/ncomms6452 · Cited by 241 · see citing works
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Anderson, A. N., Pavese, N., Edison, P., Tai, Y., Hammers, A., Gerhard, A., Brooks, D. J., & Turkheimer, F. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2007.02.017 · Cited by 42 · see citing works
Targeting the 18-kDa translocator protein: recent perspectives for neuroprotection
Pozzo, E. D., Giacomelli, C., Barresi, E., Costa, B., Taliani, S., Settimo, F. D., & Martini, C. (2015) · Biochemical Society Transactions · doi:10.1042/bst20150028 · Cited by 41 · see citing works
Cyclosporin A Provides No Sustained Immunologic Benefit to Persons with Chronic HIV‐1 Infection Starting Suppressive Antiretroviral Therapy: Results of a Randomized, Controlled Trial of the AIDS Clinical Trials Group A5138
Lederman, M. M., Smeaton, L. M., Smith, K. Y., Rodriguez, B. A., Pu, M., Wang, H., Sevin, A. D., Tebas, P., Sieg, S. F., Medvik, K., et al. (2006) · The Journal of Infectious Diseases · doi:10.1086/509261 · Cited by 39 · see citing works
Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy
Fairley, L. H., Sahara, N., Aoki, I., Ji, B., Suhara, T., Higuchi, M., & Barron, A. M. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02122-1 · Cited by 35 · see citing works
Calcium ion influx in microglial cells: Physiological and therapeutic significance
Sharma, P., & Ping, L. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23344 · Cited by 37 · see citing works
Early steps of microglial activation are directly affected by neuroprotectant FK506 in both in vitro inflammation and in rat model of stroke
Zawadzka, M., Dąbrowski, M., Góźdź, A., Szadujkis, B., Sliwa, M., Lipko, M. A., & Kaminska, B. (2012) · Journal of Molecular Medicine · doi:10.1007/s00109-012-0925-9 · Cited by 36 · see citing works
Sex Steroids, Adult Neurogenesis, and Inflammation in CNS Homeostasis, Degeneration, and Repair
Larson, T. A. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00205 · Cited by 36 · see citing works
The hGFAP-driven conditional TSPO knockout is protective in a mouse model of multiple sclerosis
Daugherty, D. J., Chechneva, O., Mayrhofer, F., & Deng, W. (2016) · Scientific Reports · doi:10.1038/srep22556 · Cited by 36 · see citing works
Mitochondrial ligand inhibits store‐operated calcium influx and COX‐2 production in human microglia
Hong, S. H., Choi, H. B., Kim, S. U., & McLarnon, J. G. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20829 · Cited by 33 · see citing works
Self-citation
Lipopolysaccharide Compromises Human Sperm Function by Reducing Intracellular cAMP
Li, Z., Zhang, D., He, Y., Ding, Z., Mao, F., Luo, T., & Zhang, X. (2016) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.238.105 · Cited by 31 · see citing works
Microarrays and expression profiling in microglia research and in inflammatory brain disorders
Gebicke‐Haerter, P. J. (2005) · Journal of Neuroscience Research · doi:10.1002/jnr.20479 · Cited by 31 · see citing works
Gut microbiota, pathogenic proteins and neurodegenerative diseases
Wei, W., Wang, S., Xu, C., Zhou, X., Lian, X., He, L., & Li, K. (2022) · Frontiers in Microbiology · doi:10.3389/fmicb.2022.959856 · Cited by 29 · see citing works
The translocator protein (TSPO) ligand PK11195 induces apoptosis and cell cycle arrest and sensitizes to chemotherapy treatment in pre- and post-relapse neuroblastoma cell lines
Mendonça-Torres, M. C., & Roberts, S. S. (2013) · Cancer Biology & Therapy · doi:10.4161/cbt.23613 · Cited by 27 · see citing works
Translocator protein and new targets for neuroinflammation
Herrera-Rivero, M., Heneka, M. T., & Papadopoulos, V. (2015) · Clinical and Translational Imaging · doi:10.1007/s40336-015-0151-x · Cited by 27 · see citing works
The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas
Takaya, S., Hashikawa, K., Turkheimer, F., Mottram, N., Deprez, M., Ishizu, K., Kawashima, H., Akiyama, H., Fukuyama, H., Banati, R. B., et al. (2007) · Journal of Neuro-Oncology · doi:10.1007/s11060-007-9396-1 · Cited by 26 · see citing works
Up‐regulation of PK11195 binding in areas of axonal degeneration coincides with early microglial activation in mouse brain
Pedersen, M. D., Minuzzi, L., Wirenfeldt, M., Meldgaard, M., Slidsborg, C., Cumming, P. D., & Finsen, B. R. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04975.x · Cited by 26 · see citing works
Platelet-activating factor enhancement of calcium influx and interleukin-6 expression, but not production, in human microglia
Sattayaprasert, P., Choi, H. B., Chongthammakun, S., & McLarnon, J. G. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-11 · Cited by 23 · see citing works
Self-citation
Inhibitory effects of glucosamine on lipopolysaccharide‐induced activation in microglial cells
Yi, H.-A., Yi, S.-D., Jang, B., Song, D., Shin, D., Mun, K., Kim, S., Suh, S., & Bae, J. H. (2005) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2005.04305.x · Cited by 20 · see citing works
Self-citation
Nuclear Imaging of Inflammation in Neurologic and Psychiatric Disorders
de Vries, E. F. J., Dierckx, R., & Klein, H. C. (2006) · Current Clinical Pharmacology · doi:10.2174/157488406778249334 · Cited by 20 · see citing works
Molecular Mechanisms of Glial Cells Related Signaling Pathways Involved in the Neuroinflammatory Response of Depression
Wang, J., Qin, J., Wang, P., Sun, Y. S., & Zhang, Q. (2020) · Mediators of Inflammation · doi:10.1155/2020/3497920 · Cited by 17 · see citing works
[11C]DAC-PET for Noninvasively Monitoring Neuroinflammation and Immunosuppressive Therapy Efficacy in Rat Experimental Autoimmune Encephalomyelitis Model
Xie, L., Yamasaki, T., Ichimaru, N., Yui, J., Kawamura, K., Kumata, K., Hatori, A., Nonomura, N., Zhang, M., Li, X., et al. (2011) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9322-3 · Cited by 18 · see citing works
Novel Microglia Cell Line Expressing the Human EP2 Receptor
Rojas, A., Banik, A., Chen, D., Flood, K., Ganesh, T., & Dingledine, R. J. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00311 · Cited by 15 · see citing works
Translocator Protein Regulate Polarization Phenotype Transformation of Microglia after Cerebral Ischemia–reperfusion Injury
Yusuying, S., Yusuyin, S., & Cheng, X. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.09.024 · Cited by 12 · see citing works
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Glucosamine suppresses platelet-activating factor-induced activation of microglia through inhibition of store-operated calcium influx
Park, J., Kim, J., Jang, B., Im, S., Song, D., & Bae, J. (2015) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2015.12.014 · Cited by 10 · see citing works
Functional role of translocator protein and its ligands in ocular diseases (Review)
Yu, M., & Zhao, S. (2024) · Molecular Medicine Reports · doi:10.3892/mmr.2024.13157 · Cited by 7 · see citing works
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Guareschi, F., Fonseca, C., Silva, S., Pescina, S., Nicoli, S., Buttini, F., Sonvico, F., & Fortuna, A. C. (2024) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2024.106994 · Cited by 7 · see citing works
Human pharmacokinetics of XBD173 and etifoxine distinguish their potential for pharmacodynamic effects mediated by translocator protein
Owen, D. R., Phillips, A. E. M., O'Connor, D. V., Grey, G., Aimola, L., Nicholas, R. S., & Matthews, P. M. (2022) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15392 · Cited by 5 · see citing works
Variation rs6971 in the Translocator Protein Gene (TSPO) is Associated with Aggressiveness and Impulsivity but Not with Anxiety in a Population-Representative Sample of Young Adults
Vaht, M. (2021) · The Journal of Genetic Psychology · doi:10.1080/00221325.2021.1896470 · Cited by 5 · see citing works
Inhibitory Activities of New Series of 4, 5-diaryl Thiadiazoles Derivatives on Lipopolysaccharide-induced Cox-2 Expression
Ostad, S. N., Amini, M., ., Z. H., Leila, K., & Navidpour, L. (2004) · International Journal of Pharmacology · doi:10.3923/ijp.2005.79.84 · Cited by 3 · see citing works
Targeting translocator protein (TSPO) ameliorates inflammation and maintains mitochondrial homeostasis to protect against dry eye
Yu, M., Xu, Y., Liu, H., Zhang, C., Yang, R., Huang, Y., Liu, Y.-C., & Zhao, S. (2026) · The Ocular Surface · doi:10.1016/j.jtos.2026.02.005 · Cited by 2 · see citing works
Understanding sedative effects within the context of acute neuroinflammation in the developing brain: Potential induction of delirium-like behaviors
Furman, A., Ferguson, N. M., Lafrenaye, A. D., Sato‐Bigbee, C., Dunbar, E. G., Sullivan, T. M., Neigh, G. N., & O'Meara, A. M. I. (2023) · Experimental Neurology · doi:10.1016/j.expneurol.2023.114453 · Cited by 2 · see citing works
17Β-ESTRADIOL AND PROGESTERONE UPREGULATE CYCLOOXYGENASE-2 EXPRESSION IN THE HUMAN GINGIVAL FIBROBLASTS
Ostad, S. N., Motahari, P., & Ghahramani, M. H. (2006) · DARU Journal of Pharmaceutical Sciences · Cited by 2 · see citing works
TSPO’nun (18 kDa Translokatör Protein) Yapısı, İşlevi ve Patolojik Süreçlerdeki Rolü
Elma, Y., & Can, E. Y. (2024) · Medical Journal of Western Black Sea · doi:10.29058/mjwbs.1477979 · Cited by 1 · see citing works
The therapeutic effects of cyclosporin-A on experimental spinal cord injury
Gezici, A. R., Kılıç, G., Fırat, T., Cancan, S. E., Kükner, A., Özkan, N., & Dağıstan, Y. (2017) · Biomedical Research-tokyo · Cited by 1 · see citing works
Effects of Anxiolytic Drugs in Animal Models of Multiple Sclerosis
Novo, S., Freire‐Garabal, M., & Jess, M. (2012) · InTech eBooks · doi:10.5772/29604
Examining the Anti-Inflammatory Characteristics of Translocator Protein Through IL-10 Modulation
Tonini, M. (2015) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Neural Substrates of Parkinson's Disease
Koshimori, Y. (2016) · TSpace (University of Toronto)
Additional file 1 of Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy
Fairley, L. H., Sahara, N., Aoki, I., Ji, B., Suhara, T., Higuchi, M., & Barron, A. M. (2021) · Figshare · doi:10.6084/m9.figshare.14252304
Translocator Protein Modulation by PK11195 and NO Synthase Inhibition Affect Cardiac Oxidative Stress and Cardiometabolic and Inflammatory Markers in Isoprenaline-Induced Rat Myocardial Injury
Ilić, A., Radisavljevic, N. M., Mutavdžin, S., Todorović, D., Boričić, N., Stankovic, S. D., Nedeljković, B. B., Matic, M. G., Stojanović, M., Škrbić, R., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27041786
BindingDB Entry 50038764: The translocator protein (18 kDa): central nervous system disease and drug design.
BindingDB (2012) · UC San Diego · doi:10.7270/q2222vp0

Inhibition of lipopolysaccharide-induced cyclooxygenase-2, tumor necrosis factor-alpha and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195.
Choi, H., Khoo, C., Ryu, J., Breemen, E. V., Kim, S., & McLarnon, J. (2002) · AJOU Open Repository (Ajou University) · Cited by 2 · see citing works
Self-citation
Two activated stages of microglia and PET imaging of peripheral benzodiazepine receptors with [11C]PK11195 in rats
Ito, F., Toyama, H., Kudo, G., Suzuki, H., Hatano, K., Ichise, M., Katada, K., Ito, K., & Sawada, M. (2010) · Annals of Nuclear Medicine · doi:10.1007/s12149-009-0339-0 · Cited by 23 · see citing works
Shigematsu A: Effect of peripheral benzodiazepine receptor ligands on lipopolysaccharide-induced tumor necrosis factor activity in thioglycolate-treated mice. Antimicrob Agents Chemother
Matsumoto, T., Ogata, M., Koga, K., & Shigematsu, A. (1994)
PKC Mediates LPS-Induced IL-1β Expression and Participates in the Pro-inflammatory Effect of A2AR Under High Glutamate Concentrations in Mouse Microglia
Fu, S.-Y., Xiong, R., Peng, Y., Zhang, Z.-H., Chen, X., Zhao, Y., Ning, Y., Yang, N., Zhou, Y., & Li, P. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02895-1 · Cited by 18 · see citing works
Effect of peripheral benzodiazepine receptor ligands on lipopolysaccharide-induced tumor necrosis factor activity in thioglycolate-treated mice
Matsumoto, T., Ogata, M., Koga, K., & Shigematsu, A. (1994) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.38.4.812 · Cited by 38 · see citing works

Authors: Choi, H. B., Khoo, C., Ryu, J. K., Van Breemen, E., Kim, S. U., & McLarnon, J. G.
Affiliations: University of British Columbia (CA)
Corresponding author: McLarnon, James G.
ORCID: Khoo, C.
Ryu, Jae K.
Kim, Seung U.
McLarnon, James G.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2002-10-17
Volume: 83
Issue: 3
Pages: 546-555
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1046/j.1471-4159.2002.01122.x
OpenAlex: W1509956998
Cited by: 82
References: 29
Citations by year: 2026: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 1 · 2016: 7 · 2015: 6 · 2014: 5 · 2013: 4 · 2012: 3
FWCI: 1.50
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Heart and Stroke Foundation of Canada
Heart and Stroke Foundation of British Columbia and Yukon
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pharmacological Receptor Mechanisms and Effects
Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Keywords: PK11195, translocator protein (TSPO), microglia, lipopolysaccharide, cyclooxygenase-2, TNF-α, intracellular calcium, anti-inflammatory activity, mitochondrial permeability transition pore, cyclosporine, neuroinflammation
MeSH terms: Brain, Calcium, Cells, Cultured, Enzyme Induction, Enzyme Inhibitors, Enzyme-Linked Immunosorbent Assay, Humans, Immunohistochemistry, Intracellular Fluid, Isoenzymes, Isoquinolines, Ligands, Lipopolysaccharides, Membrane Proteins, Mitochondria, Prostaglandin-Endoperoxide Synthases, Receptors, GABA-A, Tumor Necrosis Factor-alpha, Up-Regulation, Cyclosporine, Microglia, Cyclooxygenase 2, GABA-A Receptor Agonists

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Inhibition of lipopolysaccharide‐induced cyclooxygenase‐2, tumor necrosis factor‐α and [Ca2+]i responses in human microglia by the peripheral benzodiazepine receptor ligand PK11195

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