PPAR Research
Volume 2008 (2008), Article ID 453120, 15 pages
http://dx.doi.org/10.1155/2008/453120
Research Article
Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR- Agonists
Department of Neurobiology and Developmental Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
Received 10 March 2008; Accepted 5 May 2008
Academic Editor: Michael Racke
Copyright © 2008 Catherine Gurley et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Linked References
- C. Farina, F. Aloisi, and E. Meinl, “Astrocytes are active players in cerebral innate immunity,” Trends in Immunology, vol. 28, no. 3, pp. 138–145, 2007. View at Publisher · View at Google Scholar
- F. Aloisi, “Immune function of microglia,” Glia, vol. 36, no. 2, pp. 165–179, 2001. View at Publisher · View at Google Scholar
- U.-K. Hanisch, “Microglia as a source and target of cytokines,” Glia, vol. 40, no. 2, pp. 140–155, 2002. View at Publisher · View at Google Scholar
- Y. Dong and E. N. Benveniste, “Immune function of astrocytes,” Glia, vol. 36, no. 2, pp. 180–190, 2001. View at Publisher · View at Google Scholar
- S. Akira, S. Uematsu, and O. Takeuchi, “Pathogen recognition and innate immunity,” Cell, vol. 124, no. 4, pp. 783–801, 2006. View at Publisher · View at Google Scholar
- T. Kaisho and S. Akira, “Pleiotropic function of Toll-like receptors,” Microbes and Infection, vol. 6, no. 15, pp. 1388–1394, 2004. View at Publisher · View at Google Scholar
- S. Carpenter and L. A. J. O'Neill, “How important are Toll-like receptors for antimicrobial responses?” Cellular Microbiology, vol. 9, no. 8, pp. 1891–1901, 2007. View at Publisher · View at Google Scholar
- G. Sitia, M. Iannacone, S. Müller, M. E. Bianchi, and L. G. Guidotti, “Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice,” Journal of Leukocyte Biology, vol. 81, no. 1, pp. 100–107, 2007. View at Publisher · View at Google Scholar
- A. M. Krieg and J. Vollmer, “Toll-like receptors 7, 8, and 9: linking innate immunity to autoimmunity,” Immunological Reviews, vol. 220, no. 1, pp. 251–269, 2007. View at Publisher · View at Google Scholar
- B. J. Marsland and M. Kopf, “Toll-like receptors: paving the path to T cell-driven autoimmunity?” Current Opinion in Immunology, vol. 19, no. 6, pp. 611–614, 2007. View at Publisher · View at Google Scholar
- T. Kielian, “Toll-like receptors in central nervous system glial inflammation and homeostasis,” Journal of Neuroscience Research, vol. 83, no. 5, pp. 711–730, 2006. View at Publisher · View at Google Scholar
- P. A. Carpentier, D. S. Duncan, and S. D. Miller, “Glial toll-like receptor signaling in central nervous system infection and autoimmunity,” Brain, Behavior, and Immunity, vol. 22, no. 2, pp. 140–147, 2008. View at Publisher · View at Google Scholar
- P. H. Larsen, T. H. Holm, and T. Owens, “Toll-like receptors in brain development and homeostasis,” Science's STKE, vol. 2007, no. 402, p. pe47, 2007. View at Publisher · View at Google Scholar
- A. A. Babcock, M. Wirenfeldt, T. Holm et al., “Toll-like receptor 2 signaling in response to brain injury: an innate bridge to neuroinflammation,” Journal of Neuroscience, vol. 26, no. 49, pp. 12826–12837, 2006. View at Publisher · View at Google Scholar
- K. A. Kigerl, W. Lai, S. Rivest, R. P. Hart, A. R. Satoskar, and P. G. Popovich, “Toll-like receptor (TLR)-2 and TLR-4 regulate inflammation, gliosis, and myelin sparing after spinal cord injury,” Journal of Neurochemistry, vol. 102, no. 1, pp. 37–50, 2007. View at Publisher · View at Google Scholar
- T. Kielian and P. D. Drew, “Effects of peroxisome proliferator-activated receptor- agonists on central nervous system inflammation,” Journal of Neuroscience Research, vol. 71, no. 3, pp. 315–325, 2003. View at Publisher · View at Google Scholar
- J. N. Feige, L. Gelman, L. Michalik, B. Desvergne, and W. Wahli, “From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions,” Progress in Lipid Research, vol. 45, no. 2, pp. 120–159, 2006. View at Publisher · View at Google Scholar
- R. Kapadia, J.-H. Yi, and R. Vemuganti, “Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists,” Frontiers in Bioscience, vol. 13, no. 5, pp. 1813–1826, 2008. View at Publisher · View at Google Scholar
- R. Kostadinova, W. Wahli, and L. Michalik, “PPARs in diseases: control mechanisms of inflammation,” Current Medicinal Chemistry, vol. 12, no. 25, pp. 2995–3009, 2005. View at Publisher · View at Google Scholar
- M. T. Heneka and G. E. Landreth, “PPARs in the brain,” Biochimica et Biophysica Acta, vol. 1771, no. 8, pp. 1031–1045, 2007. View at Publisher · View at Google Scholar
- P. D. Drew, J. Xu, P. D. Storer, J. A. Chavis, and M. K. Racke, “Peroxisome proliferator-activated receptor agonist regulation of glial activation: relevance to CNS inflammatory disorders,” Neurochemistry International, vol. 49, no. 2, pp. 183–189, 2006. View at Publisher · View at Google Scholar
- A. Bernando and L. Minghetti, “PPAR- agonists as regulators of microglial activation and brain inflammation,” Current Pharmaceutical Design, vol. 12, no. 1, pp. 93–109, 2006. View at Publisher · View at Google Scholar
- T. Kielian, M. McMahon, E. D. Bearden, A. C. Baldwin, P. D. Drew, and N. Esen, “S. aureus-dependent microglial activation is selectively attenuated by the cyclopentenone prostaglandin 15-deoxy--prostaglandin (15d-PG),” Journal of Neurochemistry, vol. 90, no. 5, pp. 1163–1172, 2004. View at Publisher · View at Google Scholar
- N. K. Phulwani, D. L. Feinstein, V. Gavrilyuk, C. Akar, and T. Kielian, “15-deoxy--prostaglandin (15d-PG) and ciglitazone modulate Staphylococcus aureus-dependent astrocyte activation primarily through a PPAR--independent pathway,” Journal of Neurochemistry, vol. 99, no. 5, pp. 1389–1402, 2006. View at Publisher · View at Google Scholar
- Q. Jiang, M. Heneka, and G. E. Landreth, “The role of peroxisome proliferator-activated receptor- (PPAR) in Alzheimer's disease: therapeutic implications,” CNS Drugs, vol. 22, no. 1, pp. 1–14, 2008. View at Google Scholar
- J. Xu and P. D. Drew, “Peroxisome proliferator-activated receptor- agonists suppress the production of IL-12 family cytokines by activated glia,” Journal of Immunology, vol. 178, no. 3, pp. 1904–1913, 2007. View at Google Scholar
- P. D. Storer, J. Xu, J. Chavis, and P. D. Drew, “Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: implications for multiple sclerosis,” Journal of Neuroimmunology, vol. 161, no. 1-2, pp. 113–122, 2005. View at Publisher · View at Google Scholar
- A. Bernardo, G. Levi, and L. Minghetti, “Role of the peroxisome proliferator-activated receptor- (PPAR-) and its natural ligand 15-deoxy--prostaglandin in the regulation of microglial functions,” European Journal of Neuroscience, vol. 12, no. 7, pp. 2215–2223, 2000. View at Publisher · View at Google Scholar
- T. V. Petrova, K. T. Akama, and L. J. Van Eldik, “Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of inducible nitric-oxide synthase by 15-deoxy--prostaglandin ,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 8, pp. 4668–4673, 1999. View at Publisher · View at Google Scholar
- C. S. Jack, N. Arbour, J. Manusow et al., “TLR signaling tailors innate immune responses in human microglia and astrocytes,” Journal of Immunology, vol. 175, no. 7, pp. 4320–4330, 2005. View at Google Scholar
- P. A. Carpentier, W. S. Begolka, J. K. Olson, A. Elhofy, W. J. Karpus, and S. D. Miller, “Differential activation of astrocytes by innate and adaptive immune stimuli,” Glia, vol. 49, no. 3, pp. 360–374, 2005. View at Publisher · View at Google Scholar
- J. K. Olson and S. D. Miller, “Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs,” Journal of Immunology, vol. 173, no. 6, pp. 3916–3924, 2004. View at Google Scholar
- N. Esen, F. Y. Tanga, J. A. DeLeo, and T. Kielian, “Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus,” Journal of Neurochemistry, vol. 88, no. 3, pp. 746–758, 2004. View at Publisher · View at Google Scholar
- N. Esen and T. Kielian, “Central role for MyD88 in the responses of microglia to pathogen-associated molecular patterns,” Journal of Immunology, vol. 176, no. 11, pp. 6802–6811, 2006. View at Google Scholar
- N. Esen and T. Kielian, “Effects of low dose GM-CSF on microglial inflammatory profiles to diverse pathogen-associated molecular patterns (PAMPs),” Journal of Neuroinflammation, vol. 4, article 10, 2007. View at Publisher · View at Google Scholar
- N. Esen, D. Shuffield, M. M. Syed, and T. Kielian, “Modulation of connexin expression and gap junction communication in astrocytes by the gram-positive bacterium S. aureus,” Glia, vol. 55, no. 1, pp. 104–117, 2007. View at Publisher · View at Google Scholar
- M. Bsibsi, R. Ravid, D. Gveric, and J. M. van Noort, “Broad expression of Toll-like receptors in the human central nervous system,” Journal of Neuropathology & Experimental Neurology, vol. 61, no. 11, pp. 1013–1021, 2002. View at Google Scholar
- T. Kielian, N. Esen, and E. D. Bearden, “Toll-like receptor 2 (TLR2) is pivotal for recognition of S. aureus peptidoglycan but not intact bacteria by microglia,” Glia, vol. 49, no. 4, pp. 567–576, 2005. View at Publisher · View at Google Scholar
- S. C. Byram, M. J. Carson, C. A. DeBoy, C. J. Serpe, V. M. Sanders, and K. J. Jones, “CD4-positive T cell-mediated neuroprotection requires dual compartment antigen presentation,” Journal of Neuroscience, vol. 24, no. 18, pp. 4333–4339, 2004. View at Publisher · View at Google Scholar
- M. J. Carson, T. V. Bilousova, S. S. Puntambekar, B. Melchior, J. M. Doose, and I. M. Ethell, “A rose by any other name? The potential consequences of microglial heterogeneity during CNS health and disease,” Neurotherapeutics, vol. 4, no. 4, pp. 571–579, 2007. View at Publisher · View at Google Scholar
- N. P. Turrin and S. Rivest, “Molecular and cellular immune mediators of neuroprotection,” Molecular Neurobiology, vol. 34, no. 3, pp. 221–242, 2006. View at Publisher · View at Google Scholar
- D. Gosselin and S. Rivest, “Role of IL-1 and TNF in the brain: twenty years of progress on a Dr. Jekyll/Mr. Hyde duality of the innate immune system,” Brain, Behavior, and Immunity, vol. 21, no. 3, pp. 281–289, 2007. View at Publisher · View at Google Scholar
- K. Sriram and J. P. O'Callaghan, “Divergent roles for tumor necrosis factor- in the brain,” Journal of NeuroImmune Pharmacology, vol. 2, no. 2, pp. 140–153, 2007. View at Publisher · View at Google Scholar
- T. Kielian, “Immunopathogenesis of brain abscess,” Journal of Neuroinflammation, vol. 1, article 16, 2004. View at Publisher · View at Google Scholar
- R. Nau and W. Brück, “Neuronal injury in bacterial meningitis: mechanisms and implications for therapy,” Trends in Neurosciences, vol. 25, no. 1, pp. 38–45, 2002. View at Publisher · View at Google Scholar
- R. N. Saha and K. Pahan, “Tumor necrosis factor- at the crossroads of neuronal life and death during HIV-associated dementia,” Journal of Neurochemistry, vol. 86, no. 5, pp. 1057–1071, 2003. View at Publisher · View at Google Scholar
- R. M. Ransohoff, L. Liu, and A. E. Cardona, “Chemokines and chemokine receptors: multipurpose players in neuroinflammation,” International Review of Neurobiology, vol. 82, pp. 187–204, 2007. View at Publisher · View at Google Scholar
- A. D. Luster, “Chemokines—chemotactic cytokines that mediate inflammation,” The New England Journal of Medicine, vol. 338, no. 7, pp. 436–445, 1998. View at Publisher · View at Google Scholar
- N. M. Rebenko-Moll, L. Liu, A. Cardona, and R. M. Ransohoff, “Chemokines, mononuclear cells and the nervous system: heaven (or hell) is in the details,” Current Opinion in Immunology, vol. 18, no. 6, pp. 683–689, 2006. View at Publisher · View at Google Scholar
- T. Kielian, B. Barry, and W. F. Hickey, “CXC chemokine receptor-2 ligands are required for neutrophil-mediated host defense in experimental brain abscesses,” Journal of Immunology, vol. 166, no. 7, pp. 4634–4643, 2001. View at Google Scholar
- M. D. Bell, D. D. Taub, S. J. Kunkel et al., “Recombinant human adenovirus with rat MIP-2 gene insertion causes prolonged PMN recruitment to the murine brain,” European Journal of Neuroscience, vol. 8, no. 9, pp. 1803–1811, 1996. View at Publisher · View at Google Scholar
- R. M. Ransohoff, P. Kivisäkk, and G. Kidd, “Three or more routes for leukocyte migration into the central nervous system,” Nature Reviews Immunology, vol. 3, no. 7, pp. 569–581, 2003. View at Publisher · View at Google Scholar
- X. Zhang, J. M. Wang, W. H. Gong, N. Mukaida, and H. A. Young, “Differential regulation of chemokine gene expression by 15-deoxy- prostaglandin ,” Journal of Immunology, vol. 166, no. 12, pp. 7104–7111, 2001. View at Google Scholar
- Q. Si, M.-L. Zhao, A. C. Morgan, C. F. Brosnan, and S. C. Lee, “15-deoxy-,-prostaglandin inhibits IFN-inducible protein 10/CXC chemokine ligand 10 expression in human microglia: mechanisms and implications,” Journal of Immunology, vol. 173, no. 5, pp. 3504–3513, 2004. View at Google Scholar
- T. Kielian, “Microglia and chemokines in infectious diseases of the nervous system: views and reviews,” Frontiers in Bioscience, vol. 9, pp. 732–750, 2004. View at Publisher · View at Google Scholar
- D. J. Mahad and R. M. Ransohoff, “The role of MCP-1 (CCL2) and CCR2 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE),” Seminars in Immunology, vol. 15, no. 1, pp. 23–32, 2003. View at Publisher · View at Google Scholar
- C. J. Auch, R. N. Saha, F. G. Sheikh, X. Liu, B. L. Jacobs, and K. Pahan, “Role of protein kinase R in double-stranded RNA-induced expression of nitric oxide synthase in human astroglia,” FEBS Letters, vol. 563, no. 1–3, pp. 223–228, 2004. View at Publisher · View at Google Scholar
- M. Ricote, A. C. Li, T. M. Willson, C. J. Kelly, and C. K. Glass, “The peroxisome proliferator-activated receptor- is a negative regulator of macrophage activation,” Nature, vol. 391, no. 6662, pp. 79–82, 1998. View at Publisher · View at Google Scholar
- D. S. Straus and C. K. Glass, “Cyclopentenone prostaglandins: new insights on biological activities and cellular targets,” Medicinal Research Reviews, vol. 21, no. 3, pp. 185–210, 2001. View at Publisher · View at Google Scholar
- L. Van Gaal and A. J. Scheen, “Are all glitazones the same?” Diabetes/Metabolism Research and Reviews, vol. 18, supplement 2, pp. S1–S4, 2002. View at Publisher · View at Google Scholar
- T. M. Willson, J. E. Cobb, D. J. Cowan et al., “The structure-activity relationship between peroxisome proliferator-activated receptor agonism and the antihyperglycemic activity of thiazolidinediones,” Journal of Medicinal Chemistry, vol. 39, no. 3, pp. 665–668, 1996. View at Google Scholar
- J. M. Lehmann, L. B. Moore, T. A. Smith-Oliver, W. O. Wilkison, T. M. Willson, and S. A. Kliewer, “An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor (PPAR),” Journal of Biological Chemistry, vol. 270, no. 22, pp. 12953–12956, 1995. View at Publisher · View at Google Scholar
- C. Dello Russo, V. Gavrilyuk, G. Weinberg et al., “Peroxisome proliferator-activated receptor thiazolidinedione agonists increase glucose metabolism in astrocytes,” Journal of Biological Chemistry, vol. 278, no. 8, pp. 5828–5836, 2003. View at Publisher · View at Google Scholar
- D. L. Feinstein, A. Spagnolo, C. Akar et al., “Receptor-independent actions of PPAR thiazolidinedione agonists: is mitochondrial function the key?” Biochemical Pharmacology, vol. 70, no. 2, pp. 177–188, 2005. View at Publisher · View at Google Scholar
- Y. Kodera, K. Takeyama, A. Murayama, M. Suzawa, Y. Masuhiro, and S. Kato, “Ligand type-specific interactions of peroxisome proliferator-activated receptor with transcriptional coactivators,” Journal of Biological Chemistry, vol. 275, no. 43, pp. 33201–33204, 2000. View at Publisher · View at Google Scholar
- P. D. Drew and J. A. Chavis, “The cyclopentone prostaglandin 15-deoxy- prostaglandin represses nitric oxide, TNF-, and IL-12 production by microglial cells,” Journal of Neuroimmunology, vol. 115, no. 1-2, pp. 28–35, 2001. View at Publisher · View at Google Scholar
- D. W. Gilroy, P. R. Colville-Nash, D. Willis, J. Chivers, M. J. Paul-Clark, and D. A. Willoughby, “Inducible cyclooxygenase may have anti-inflammatory properties,” Nature Medicine, vol. 5, no. 6, pp. 698–701, 1999. View at Publisher · View at Google Scholar
- T. Lawrence, D. A. Willoughby, and D. W. Gilroy, “Anti-inflammatory lipid mediators and insights into the resolution of inflammation,” Nature Reviews Immunology, vol. 2, no. 10, pp. 787–795, 2002. View at Publisher · View at Google Scholar
- C. L. Langrish, B. S. McKenzie, N. J. Wilson, R. de Waal Malefyt, R. A. Kastelein, and D. J. Cua, “IL-12 and IL-23: master regulators of innate and adaptive immunity,” Immunological Reviews, vol. 202, no. 1, pp. 96–105, 2004. View at Publisher · View at Google Scholar
- G. Trinchieri, “Interleukin-12 and the regulation of innate resistance and adaptive immunity,” Nature Reviews Immunology, vol. 3, no. 2, pp. 133–146, 2003. View at Publisher · View at Google Scholar
- T. Kielian, M. M. Syed, S. Liu et al., “The synthetic PPAR- agonist ciglitazone attenuates neuroinflammation and accelerates encapsulation in bacterial brain abscesses,” Journal of immunology, vol. 180, no. 3, pp. 5004–5016, 2008. View at Google Scholar
- A. von Knethen, M. Soller, and B. Brüne, “Peroxisome proliferator-activated receptor (PPAR) and sepsis,” Archivum Immunologiae et Therapiae Experimentalis, vol. 55, no. 1, pp. 19–25, 2007. View at Publisher · View at Google Scholar
- R. Arnold and W. König, “Peroxisome proliferator-activated receptor- agonists inhibit the replication of respiratory syncytial virus (RSV) in human lung epithelial cells,” Virology, vol. 350, no. 2, pp. 335–346, 2006. View at Publisher · View at Google Scholar
- D. Liu, B. X. Zeng, S. H. Zhang, and S. L. Yao, “Rosiglitazone, an agonist of peroxisome proliferator-activated receptor , reduces pulmonary inflammatory response in a rat model of endotoxemia,” Inflammation Research, vol. 54, no. 11, pp. 464–470, 2005. View at Publisher · View at Google Scholar
- J. M. Kaplan, J. A. Cook, P. W. Hake, M. O'Connor, T. J. Burroughs, and B. Zingarelli, “15-deoxy--prostaglandin (15D-PG), a peroxisome proliferator activated receptor ligand, reduces tissue leukosequestration and mortality in endotoxic shock,” Shock, vol. 24, no. 1, pp. 59–65, 2005. View at Publisher · View at Google Scholar
- S. H. Ramirez, D. Heilman, B. Morsey, R. Potula, J. Haorah, and Y. Persidsky, “Activation of peroxisome proliferator-activated receptor (PPAR) suppresses Rho GTPases in human brain microvascular endothelial cells and inhibits adhesion and transendothelial migration of HIV-1 infected monocytes,” Journal of immunology, vol. 180, no. 3, pp. 1854–1865, 2008. View at Google Scholar