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Chikungunya virus (CHIKV) is a re-emerging, mosquito-transmitted, enveloped positive stranded RNA virus. Chikungunya fever is characterized by acute and chronic debilitating arthritis. Although multiple host factors have been shown to enhance CHIKV infection, the molecular mechanisms of cell entry and entry factors remain poorly understood. The phosphatidylserine-dependent receptors, T-cell immunoglobulin and mucin domain 1 (TIM-1) and Axl receptor tyrosine kinase (Axl), are transmembrane proteins that can serve as entry factors for enveloped viruses. Previous studies used pseudoviruses to delineate the role of TIM-1 and Axl in CHIKV entry. Conversely, here, we use the authentic CHIKV and cells ectopically expressing TIM-1 or Axl and demonstrate a role for TIM-1 in CHIKV infection. To further characterize TIM-1-dependent CHIKV infection, we generated cells expressing domain mutants of TIM-1. We show that point mutations in the phosphatidylserine binding site of TIM-1 lead to reduced cell binding, entry, and infection of CHIKV. Ectopic expression of TIM-1 renders immortalized keratinocytes permissive to CHIKV, whereas silencing of endogenously expressed TIM-1 in human hepatoma cells reduces CHIKV infection. Altogether, our findings indicate that, unlike Axl, TIM-1 readily promotes the productive entry of authentic CHIKV into target cells.
Jared Kirui; Yara Abidine; AnnaSara Lenman; Koushikul Islam; Yong-Dae Gwon; Lisa Lasswitz; Magnus Evander; Marta Bally; Gisa Gerold. The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry. Cells 2021, 10, 1828 .
AMA StyleJared Kirui, Yara Abidine, AnnaSara Lenman, Koushikul Islam, Yong-Dae Gwon, Lisa Lasswitz, Magnus Evander, Marta Bally, Gisa Gerold. The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry. Cells. 2021; 10 (7):1828.
Chicago/Turabian StyleJared Kirui; Yara Abidine; AnnaSara Lenman; Koushikul Islam; Yong-Dae Gwon; Lisa Lasswitz; Magnus Evander; Marta Bally; Gisa Gerold. 2021. "The Phosphatidylserine Receptor TIM-1 Enhances Authentic Chikungunya Virus Cell Entry." Cells 10, no. 7: 1828.
Adenovirus is a common cause of disease in humans and in animals
Niklas Arnberg; AnnaSara Lenman. Special Issue “Adenovirus Pathogenesis”. Viruses 2021, 13, 1112 .
AMA StyleNiklas Arnberg, AnnaSara Lenman. Special Issue “Adenovirus Pathogenesis”. Viruses. 2021; 13 (6):1112.
Chicago/Turabian StyleNiklas Arnberg; AnnaSara Lenman. 2021. "Special Issue “Adenovirus Pathogenesis”." Viruses 13, no. 6: 1112.
Human adenovirus (HAdV)-F40 and -F41 are leading causes of diarrhea and diarrhea-associated mortality in children under the age of five, but the mechanisms by which they infect host cells are poorly understood. HAdVs initiate infection through interactions between the knob domain of the fiber capsid protein and host cell receptors. Unlike most other HAdVs, HAdV-F40 and -F41 possess two different fiber proteins—a long fiber and a short fiber. Whereas the long fiber binds to the Coxsackievirus and adenovirus receptor (CAR), no binding partners have been identified for the short fiber. In this study, we identified heparan sulfate (HS) as an interaction partner for the short fiber of enteric HAdVs. We demonstrate that exposure to acidic pH, which mimics the environment of the stomach, inactivates the interaction of enteric adenovirus with CAR. However, the short fiber:HS interaction is resistant to and even enhanced by acidic pH, which allows attachment to host cells. Our results suggest a switch in receptor usage of enteric HAdVs after exposure to acidic pH and add to the understanding of the function of the short fibers. These results may also be useful for antiviral drug development and the utilization of enteric HAdVs for clinical applications such as vaccine development.
Anandi Rajan; Elin Palm; Fredrik Trulsson; Sarah Mundigl; Miriam Becker; B. Persson; Lars Frängsmyr; AnnaSara Lenman. Heparan Sulfate Is a Cellular Receptor for Enteric Human Adenoviruses. Viruses 2021, 13, 298 .
AMA StyleAnandi Rajan, Elin Palm, Fredrik Trulsson, Sarah Mundigl, Miriam Becker, B. Persson, Lars Frängsmyr, AnnaSara Lenman. Heparan Sulfate Is a Cellular Receptor for Enteric Human Adenoviruses. Viruses. 2021; 13 (2):298.
Chicago/Turabian StyleAnandi Rajan; Elin Palm; Fredrik Trulsson; Sarah Mundigl; Miriam Becker; B. Persson; Lars Frängsmyr; AnnaSara Lenman. 2021. "Heparan Sulfate Is a Cellular Receptor for Enteric Human Adenoviruses." Viruses 13, no. 2: 298.
Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ notably in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here, we present the first structure of an enteric HAdV—HAdV-F41—determined by cryo–electron microscopy to a resolution of 3.8 Å. The structure reveals extensive alterations to the virion exterior as compared to nonenteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of core protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation of enteric HAdVs to a fundamentally different tissue tropism.
K. Rafie; A. Lenman; J. Fuchs; A. Rajan; N. Arnberg; L.-A. Carlson. The structure of enteric human adenovirus 41—A leading cause of diarrhea in children. Science Advances 2021, 7, eabe0974 .
AMA StyleK. Rafie, A. Lenman, J. Fuchs, A. Rajan, N. Arnberg, L.-A. Carlson. The structure of enteric human adenovirus 41—A leading cause of diarrhea in children. Science Advances. 2021; 7 (2):eabe0974.
Chicago/Turabian StyleK. Rafie; A. Lenman; J. Fuchs; A. Rajan; N. Arnberg; L.-A. Carlson. 2021. "The structure of enteric human adenovirus 41—A leading cause of diarrhea in children." Science Advances 7, no. 2: eabe0974.
Many viruses enter target cells using cell adhesion molecules as receptors. Paradoxically, these molecules are abundant on the lateral and basolateral side of intact, polarized, epithelial target cells, but absent on the apical side that must be penetrated by incoming viruses to initiate infection. Our study provides a model whereby viruses use different mechanisms to infect polarized epithelial cells depending on which side of the cell—apical or lateral/basolateral—is attacked. This study may also be useful to understand the biology of other viruses that use cell adhesion molecules as receptors.
B. David Persson; AnnaSara Lenman; Lars Frängsmyr; Markus Schmid; Clas Ahlm; Andreas Plückthun; Håvard Jenssen; Niklas Arnberg. Lactoferrin-Hexon Interactions Mediate CAR-Independent Adenovirus Infection of Human Respiratory Cells. Journal of Virology 2020, 94, 1 .
AMA StyleB. David Persson, AnnaSara Lenman, Lars Frängsmyr, Markus Schmid, Clas Ahlm, Andreas Plückthun, Håvard Jenssen, Niklas Arnberg. Lactoferrin-Hexon Interactions Mediate CAR-Independent Adenovirus Infection of Human Respiratory Cells. Journal of Virology. 2020; 94 (14):1.
Chicago/Turabian StyleB. David Persson; AnnaSara Lenman; Lars Frängsmyr; Markus Schmid; Clas Ahlm; Andreas Plückthun; Håvard Jenssen; Niklas Arnberg. 2020. "Lactoferrin-Hexon Interactions Mediate CAR-Independent Adenovirus Infection of Human Respiratory Cells." Journal of Virology 94, no. 14: 1.
Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ strikingly in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here we present the first structure of an enteric HAdV - HAdV-F41 - determined by cryo-EM to a resolution of 3.8Å. The structure reveals extensive alterations to the virion exterior as compared to non-enteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation to a fundamentally different tissue tropism of enteric HAdVs.
Karim Rafie; AnnaSara Lenman; Johannes Fuchs; Anandi Rajan; Niklas Arnberg; Lars-Anders Carlson. The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children. 2020, 1 .
AMA StyleKarim Rafie, AnnaSara Lenman, Johannes Fuchs, Anandi Rajan, Niklas Arnberg, Lars-Anders Carlson. The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children. . 2020; ():1.
Chicago/Turabian StyleKarim Rafie; AnnaSara Lenman; Johannes Fuchs; Anandi Rajan; Niklas Arnberg; Lars-Anders Carlson. 2020. "The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children." , no. : 1.
Novel tick-borne phleboviruses in the Phenuiviridae family, which are highly pathogenic in humans and all closely related to Uukuniemi virus (UUKV), have recently emerged on different continents. How phleboviruses assemble, bud, and exit cells remains largely elusive. Here, we performed high-resolution, label-free mass spectrometry analysis of UUKV immunoprecipitated from cell lysates and identified 39 cellular partners interacting with the viral envelope glycoproteins. The importance of these host factors for UUKV infection was validated by silencing each host factor by RNA interference. This revealed Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1), a guanine nucleotide exchange factor resident in the Golgi, as a critical host factor required for the UUKV life cycle. An inhibitor of GBF1, Golgicide A, confirmed the role of the cellular factor in UUKV infection. We could pinpoint the GBF1 requirement to UUKV replication and particle assembly. When the investigation was extended to viruses from various positive and negative RNA viral families, we found that not only phleboviruses rely on GBF1 for infection, but also Flavi-, Corona-, Rhabdo-, and Togaviridae. In contrast, silencing or blocking GBF1 did not abrogate infection by the human adenovirus serotype 5 and immunodeficiency retrovirus type 1, the replication of both requires nuclear steps. Together our results indicate that UUKV relies on GBF1 for viral replication, assembly and egress. This study also highlights the proviral activity of GBF1 in the infection by a broad range of important zoonotic RNA viruses. Graphical Abstract Highlights Quantitative proteomics reveals GBF1 to interact with Uukuniemi virus glycoproteins. GBF1 is a proviral host factor for phleboviruses and other zoonotic RNA viruses. GBF1 supports phlebovirus replication and assembly and release of particles. The GBF1 inhibitor Golgicide A blocks infection with zoonotic RNA viruses.
Zina M. Uckeley; Rebecca Moeller; Lars I. Kühn; Emma Nilsson; Claudia Robens; Lisa Lasswitz; Richard Lindqvist; AnnaSara Lenman; Vania Passos; Yannik Voss; Christian Sommerauer; Martin Kampmann; Christine Goffinet; Felix Meissner; Anna K. Överby; Pierre-Yves Lozach; Gisa Gerold. Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses. Molecular & Cellular Proteomics 2019, 18, 2401 -2417.
AMA StyleZina M. Uckeley, Rebecca Moeller, Lars I. Kühn, Emma Nilsson, Claudia Robens, Lisa Lasswitz, Richard Lindqvist, AnnaSara Lenman, Vania Passos, Yannik Voss, Christian Sommerauer, Martin Kampmann, Christine Goffinet, Felix Meissner, Anna K. Överby, Pierre-Yves Lozach, Gisa Gerold. Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses. Molecular & Cellular Proteomics. 2019; 18 (12):2401-2417.
Chicago/Turabian StyleZina M. Uckeley; Rebecca Moeller; Lars I. Kühn; Emma Nilsson; Claudia Robens; Lisa Lasswitz; Richard Lindqvist; AnnaSara Lenman; Vania Passos; Yannik Voss; Christian Sommerauer; Martin Kampmann; Christine Goffinet; Felix Meissner; Anna K. Överby; Pierre-Yves Lozach; Gisa Gerold. 2019. "Quantitative Proteomics of Uukuniemi Virus-host Cell Interactions Reveals GBF1 as Proviral Host Factor for Phleboviruses." Molecular & Cellular Proteomics 18, no. 12: 2401-2417.
Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein–carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members ofHuman mastadenovirus G.
AnnaSara Lenman; A. Manuel Liaci; Yan Liu; Lars Frängsmyr; Martin Frank; Baerbel Blaum; Wengang Chai; Iva Podgorski; Balázs Harrach; Mária Benkő; Ten Feizi; Thilo Stehle; Niklas Arnberg. Polysialic acid is a cellular receptor for human adenovirus 52. Proceedings of the National Academy of Sciences 2018, 115, E4264 -E4273.
AMA StyleAnnaSara Lenman, A. Manuel Liaci, Yan Liu, Lars Frängsmyr, Martin Frank, Baerbel Blaum, Wengang Chai, Iva Podgorski, Balázs Harrach, Mária Benkő, Ten Feizi, Thilo Stehle, Niklas Arnberg. Polysialic acid is a cellular receptor for human adenovirus 52. Proceedings of the National Academy of Sciences. 2018; 115 (18):E4264-E4273.
Chicago/Turabian StyleAnnaSara Lenman; A. Manuel Liaci; Yan Liu; Lars Frängsmyr; Martin Frank; Baerbel Blaum; Wengang Chai; Iva Podgorski; Balázs Harrach; Mária Benkő; Ten Feizi; Thilo Stehle; Niklas Arnberg. 2018. "Polysialic acid is a cellular receptor for human adenovirus 52." Proceedings of the National Academy of Sciences 115, no. 18: E4264-E4273.
Most adenoviruses attach to host cells by means of the protruding fiber protein that binds to host cells via the coxsackievirus and adenovirus receptor (CAR) protein. Human adenovirus type 52 (HAdV-52) is one of only three gastroenteritis-causing HAdVs that are equipped with two different fiber proteins, one long and one short. Here we show, by means of virion-cell binding and infection experiments, that HAdV-52 can also attach to host cells via CAR, but most of the binding depends on sialylated glycoproteins. Glycan microarray, flow cytometry, surface plasmon resonance and ELISA analyses reveal that the terminal knob domain of the long fiber (52LFK) binds to CAR, and the knob domain of the short fiber (52SFK) binds to sialylated glycoproteins. X-ray crystallographic analysis of 52SFK in complex with 2-O-methylated sialic acid combined with functional studies of knob mutants revealed a new sialic acid binding site compared to other, known adenovirus:glycan interactions. Our findings shed light on adenovirus biology and may help to improve targeting of adenovirus-based vectors for gene therapy. HAdVs are common pathogens in humans, causing disease mainly in eyes, airways and gastrointestinal tract. Most HAdVs are equipped with twelve protruding fiber proteins that mediate attachment to host cell receptor molecules. Recently, a new human gastroenteritis-associated adenovirus (HAdV-52) was identified and classified as the first member of a novel species (HAdV-G). Unlike most other HAdVs, this virus contains two different fiber proteins, a long and a short one, a feature shared only with the two members of species HAdV-F (HAdV-40 and -41). To gain further insights into the mechanisms of HAdV-52 infection of human cells, we set out to identify the host cell receptors used by the long and short fibers. We find that the long fiber binds to a protein-based receptor known as the coxsackievirus and adenovirus receptor (CAR), and that the short fiber binds to glycoproteins that contain sialic acid-capped glycans. The crystal structure determination of a complex of the short fiber knob bound to sialic acid demonstrates that this interaction is unique among HAdVs, and bioinformatic analysis indicates that simian AdVs may also engage sialic acids in the manner seen in HAdV-52. The results presented here provide insights into the plasticity of adenovirus-host cell interactions.
AnnaSara Lenman; A. Manuel Liaci; Yan Liu; Carin Årdahl; Anandi Rajan; Emma Nilsson; Will Bradford; Lisa Kaeshammer; Morris S. Jones; Lars Frängsmyr; Ten Feizi; Thilo Stehle; Niklas Arnberg. Human Adenovirus 52 Uses Sialic Acid-containing Glycoproteins and the Coxsackie and Adenovirus Receptor for Binding to Target Cells. PLOS Pathogens 2015, 11, e1004657 .
AMA StyleAnnaSara Lenman, A. Manuel Liaci, Yan Liu, Carin Årdahl, Anandi Rajan, Emma Nilsson, Will Bradford, Lisa Kaeshammer, Morris S. Jones, Lars Frängsmyr, Ten Feizi, Thilo Stehle, Niklas Arnberg. Human Adenovirus 52 Uses Sialic Acid-containing Glycoproteins and the Coxsackie and Adenovirus Receptor for Binding to Target Cells. PLOS Pathogens. 2015; 11 (2):e1004657.
Chicago/Turabian StyleAnnaSara Lenman; A. Manuel Liaci; Yan Liu; Carin Årdahl; Anandi Rajan; Emma Nilsson; Will Bradford; Lisa Kaeshammer; Morris S. Jones; Lars Frängsmyr; Ten Feizi; Thilo Stehle; Niklas Arnberg. 2015. "Human Adenovirus 52 Uses Sialic Acid-containing Glycoproteins and the Coxsackie and Adenovirus Receptor for Binding to Target Cells." PLOS Pathogens 11, no. 2: e1004657.
Human species A adenoviruses (HAdVs) comprise three serotypes: HAdV-12, -18, and -31. These viruses are common pathogens and cause systemic infections that usually involve the airways and/or intestine. In immunocompromised individuals, species A adenoviruses in general, and HAdV-31 in particular, cause life-threatening infections. By combining binding and infection experiments, we demonstrate that coagulation factor IX (FIX) efficiently enhances binding and infection by HAdV-18 and HAdV-31, but not by HAdV-12, in epithelial cells originating from the airways or intestine. This is markedly different from the mechanism for HAdV-5 and other human adenoviruses, which utilize coagulation factor X (FX) for infection of host cells. Surface plasmon resonance experiments revealed that the affinity of the HAdV-31 hexon-FIX interaction is higher than that of the HAdV-5 hexon-FX interaction and that the half-lives of these interactions are profoundly different. Moreover, both HAdV-31-FIX and HAdV-5-FX complexes bind to heparan sulfate-containing glycosaminoglycans (GAGs) on target cells, but binding studies utilizing cells expressing specific GAGs and GAG-cleaving enzymes revealed differences in GAG dependence and specificity between these two complexes. These findings add to our understanding of the intricate infection pathways used by human adenoviruses, and they may contribute to better design of HAdV-based vectors for gene and cancer therapy. Furthermore, the interaction between the HAdV-31 hexon and FIX may also serve as a target for antiviral treatment.
AnnaSara Lenman; Steffen Müller; Mari I. Nygren; Lars Frängsmyr; Thilo Stehle; Niklas Arnberg. Coagulation Factor IX Mediates Serotype-Specific Binding of Species A Adenoviruses to Host Cells. Journal of Virology 2011, 85, 13420 -13431.
AMA StyleAnnaSara Lenman, Steffen Müller, Mari I. Nygren, Lars Frängsmyr, Thilo Stehle, Niklas Arnberg. Coagulation Factor IX Mediates Serotype-Specific Binding of Species A Adenoviruses to Host Cells. Journal of Virology. 2011; 85 (24):13420-13431.
Chicago/Turabian StyleAnnaSara Lenman; Steffen Müller; Mari I. Nygren; Lars Frängsmyr; Thilo Stehle; Niklas Arnberg. 2011. "Coagulation Factor IX Mediates Serotype-Specific Binding of Species A Adenoviruses to Host Cells." Journal of Virology 85, no. 24: 13420-13431.
Most adenoviruses bind directly to the coxsackie and adenovirus receptor (CAR) on target cells in vitro, but recent research has shown that adenoviruses can also use soluble components in body fluids for indirect binding to target cells. These mechanisms have been identified upon addressing the questions of how to de- and retarget adenovirus-based vectors for human gene and cancer therapy, but the newly identified mechanisms also suggest that the role of body fluids and their components may also be of importance for natural, primary infections. Here we demonstrate that plasma, saliva, and tear fluid promote binding and infection of adenovirus type 5 (Ad5) in respiratory and ocular epithelial cells, which corresponds to the natural tropism of most adenoviruses, and that plasma promotes infection by Ad31. By using a set of binding and infection experiments, we also found that Ad5 and Ad31 require coagulation factors IX (FIX) or X (FX) or just FIX, respectively, for efficient binding and infection. The concentrations of these factors that were required for maximum binding were 1/100th of the physiological concentrations. Preincubation of virions with heparin or pretreatment of cells with heparinase I indicated that the role of cell surface heparan sulfate during FIX- and FX-mediated adenovirus binding and infection is mechanistically serotype specific. We conclude that the use of coagulation factors by adenoviruses may be of importance not only for the liver tropism seen when administering adenovirus vectors to the circulation but also during primary infections by wild-type viruses of their natural target cell types.
Mari I. Jonsson; Annasara E. Lenman; Lars Frängsmyr; Cecilia Nyberg; Mohamed Abdullahi; Niklas Arnberg. Coagulation Factors IX and X Enhance Binding and Infection of Adenovirus Types 5 and 31 in Human Epithelial Cells. Journal of Virology 2009, 83, 3816 -3825.
AMA StyleMari I. Jonsson, Annasara E. Lenman, Lars Frängsmyr, Cecilia Nyberg, Mohamed Abdullahi, Niklas Arnberg. Coagulation Factors IX and X Enhance Binding and Infection of Adenovirus Types 5 and 31 in Human Epithelial Cells. Journal of Virology. 2009; 83 (8):3816-3825.
Chicago/Turabian StyleMari I. Jonsson; Annasara E. Lenman; Lars Frängsmyr; Cecilia Nyberg; Mohamed Abdullahi; Niklas Arnberg. 2009. "Coagulation Factors IX and X Enhance Binding and Infection of Adenovirus Types 5 and 31 in Human Epithelial Cells." Journal of Virology 83, no. 8: 3816-3825.
There is good evidence that agents interacting with the endocannabinoid system in the body can also interact with the peroxisome proliferator‐activated receptor γ. The present study was designed to test whether the reverse is true, namely whether peroxisome proliferator‐activated receptor γ ligands have direct effects upon the activity of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase. Fatty acid amide hydrolase activity was measured in rat brain homogenates, C6 glioma and RBL2H3 basophilic leukaemia cells. Cellular uptake of anandamide was also assessed in these cells. Peroxisome proliferator‐activated receptor γ activators inhibited the metabolism of the endocannabinoid anandamide in rat brain homogenates with an order of potency MCC‐555 > indomethacin ≈ ciglitazone ≈ 15‐deoxy‐Δ12,14‐prostaglandin J2 ≈ pioglitazone > rosiglitazone > troglitazone. The antagonists BADGE, GW9662 and T0070907 were poor inhibitors of anandamide hydrolysis. The inhibition by ciglitazone was competitive and increased as the pH of the assay buffer was decreased; the Ki value at pH 6.0 was 17 μM. In intact C6 glioma cells assayed at pH 6.2, significant inhibition of anandamide hydrolysis was seen at 3 μM ciglitazone, whereas 100 μM was required to produce significant inhibition at pH 7.4. Ciglitazone also interacted with monoacylglycerol lipase as well as with cannabinoid CB1 and CB2 receptors. Ciglitazone may be useful as a template for the design of novel dual action anti‐inflammatory agents which are both inhibitors of fatty acid amide hydrolase and agonists at the peroxisome proliferator‐activated receptor γ. British Journal of Pharmacology (2007) 151, 1343–1351; doi:10.1038/sj.bjp.0707352
AnnaSara Lenman; C J Fowler. Interaction of ligands for the peroxisome proliferator-activated receptor γ with the endocannabinoid system. British Journal of Pharmacology 2007, 151, 1343 -1351.
AMA StyleAnnaSara Lenman, C J Fowler. Interaction of ligands for the peroxisome proliferator-activated receptor γ with the endocannabinoid system. British Journal of Pharmacology. 2007; 151 (8):1343-1351.
Chicago/Turabian StyleAnnaSara Lenman; C J Fowler. 2007. "Interaction of ligands for the peroxisome proliferator-activated receptor γ with the endocannabinoid system." British Journal of Pharmacology 151, no. 8: 1343-1351.