Autotaxin Downregulates LPS-Induced Microglia Activation and Pro-Inflammatory Cytokines Production

被引:51
作者
Awada, Rana [1 ]
Saulnier-Blache, Jean Sebastien [2 ]
Gres, Sandra [2 ]
Bourdon, Emmanuel [1 ]
Rondeau, Philippe [1 ]
Parimisetty, Avinash [1 ]
Orihuela, Ruben [3 ]
Harry, G. Jean [3 ]
d'Hellencourt, Christian Lefebvre [1 ]
机构
[1] Univ La Reunion, GEICO, EA 4516, St Clothilde, Reunion, France
[2] Inst Malad Metab & Cardiovasc I2MC, INSERM, U1048, Toulouse 4, France
[3] NIEHS, Neurotoxicol Grp, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA
关键词
AUTOTAXIN; MICROGLIA; INFLAMMATION; LYSOPHOSPHATIDIC ACID; CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; LYSOPHOSPHATIDIC ACID PRODUCTION; LYSOPHOSPHOLIPASE-D; MULTIPLE-SCLEROSIS; INTERFERON-GAMMA; FACTOR-ALPHA; THP-1; CELLS; EXPRESSION; RECEPTORS;
D O I
10.1002/jcb.24889
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inflammation is essential in defense against infection or injury. It is tightly regulated, as over-response can be detrimental, especially in immune-privileged organs such as the central nervous system (CNS). Microglia constitutes the major source of inflammatory factors, but are also involved in the regulation of the inflammation and in the reparation. Autotaxin (ATX), a phospholipase D, converts lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA) and is upregulated in several CNS injuries. LPA, a pleiotropic immunomodulatory factor, can induce multiple cellular processes including morphological changes, proliferation, death, and survival. We investigated ATX effects on microglia inflammatory response to lipopolysaccharide (LPS), mimicking gram-negative infection. Murine BV-2 microglia and stable transfected, overexpressing ATX-BV-2 (A+) microglia were treated with LPS. Tumor necrosis factor (TNF), interleukin (IL)-6, and IL-10 mRNA and proteins levels were examined by qRT-PCR and ELISA, respectively. Secreted LPA was quantified by a radioenzymatic assay and microglial activation markers (CD11b, CD14, B7.1, and B7.2) were determined by flow cytometry. ATX expression and LPA production were significantly enhanced in LPS treated BV-2 cells. LPS induction of mRNA and protein level for TNF and IL-6 were inhibited in A+ cells, while IL-10 was increased. CD11b, CD14, and B7.1, and B7.2 expressions were reduced in A+ cells. Our results strongly suggest deactivation of microglia and an IL-10 inhibitory of ATX with LPS induced microglia activation. J. Cell. Biochem. 115: 2123-2132, 2014. (c) 2014 Wiley Periodicals, Inc.
引用
收藏
页码:2123 / 2132
页数:10
相关论文
共 47 条
[1]   Microglia: Scapegoat, Saboteur, or Something Else? [J].
Aguzzi, Adriano ;
Barres, Ben A. ;
Bennett, Mariko L. .
SCIENCE, 2013, 339 (6116) :156-161
[2]  
Aloisi F, 1999, J NEUROSCI RES, V56, P571
[3]   Autotaxin protects microglial cells against oxidative stress [J].
Awada, Rana ;
Rondeau, Philippe ;
Gres, Sandra ;
Saulnier-Blache, Jean Sebastien ;
d'Hellencourt, Christian Lefebvre ;
Bourdon, Emmanuel .
FREE RADICAL BIOLOGY AND MEDICINE, 2012, 52 (02) :516-526
[4]   Review: Activation patterns of microglia and their identification in the human brain [J].
Boche, D. ;
Perry, V. H. ;
Nicoll, J. A. R. .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2013, 39 (01) :3-18
[5]   Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors [J].
Bruce, AJ ;
Boling, W ;
Kindy, MS ;
Peschon, J ;
Kraemer, PJ ;
Carpenter, MK ;
Holtsberg, FW ;
Mattson, MP .
NATURE MEDICINE, 1996, 2 (07) :788-794
[6]   Microglia-derived tumor necrosis factor-α exaggerates death of newborn hippocampal progenitor cells in vitro [J].
Cacci, E ;
Claasen, JH ;
Kokaia, Z .
JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 80 (06) :789-797
[7]   Macrophage-mediated inflammation in metabolic disease [J].
Chawla, Ajay ;
Nguyen, Khoa D. ;
Goh, Y. P. Sharon .
NATURE REVIEWS IMMUNOLOGY, 2011, 11 (11) :738-749
[8]   Inflammation and gliosis in neurological diseases - clinical implications [J].
Czlonkowska, Anna ;
Kurkowska-Jastrzebska, Iwona .
JOURNAL OF NEUROIMMUNOLOGY, 2011, 231 (1-2) :78-85
[9]   Lysophosphatidic acid inhibits bacterial endotoxin-induced pro-inflammatory response: Potential anti-inflammatory signaling pathways [J].
Fan, Hongkuan ;
Zingarelli, Basilia ;
Harris, Vashaunta ;
Tempel, George E. ;
Halushka, Perry V. ;
Cook, James A. .
MOLECULAR MEDICINE, 2008, 14 (7-8) :422-428
[10]   Therapeutic potential of autotaxin/lysophospholipase D inhibitors [J].
Federico, Lorenzo ;
Pamuklar, Zehra ;
Smyth, Susan S. ;
Morris, Andrew J. .
CURRENT DRUG TARGETS, 2008, 9 (08) :698-708