Anti-inflammatory effects of autotaxin on microglial cells

Abstract : Inflammation is essential in defence against infection or injury.However, overresponse can be detrimental, especially in immune-privileged organs such as the central nervous system, in whichmicroglia are the major source of inflammatory factors. Auto-taxin (ATX), a phospholipase D, converts lysophosphatidylcho-line into lysophosphatidic acid (LPA) and is upregulated inseveral CNS injuries. LPA, a pleiotropic immunomodulatory fac-tor, can induce multiple cellular processes, morphology, prolifera-tion, death and survival. Here, we investigated ATX effects onthe inflammatory response to two distinct inflammatory stimulitargeting microglia. Lipopolysacharide (LPS) mimics gram nega-tive infection, and trimethyltin (TMT), induces hippocampal neu-rodegeneration via the tumor necrosis factor (TNF) pathway.Murine BV2 microglia and stable transfected, overexpressingATX BV2 (BV2A+) were treated with LPS (1lg) and TMT(10lM). ATX, TNF, interleukin (IL)-6, IL-10 levels were exam-ined by qRT-PCR. LPA levels were determined. Microglial acti-vation markers (CD11b, CD14, B7.1, B7.2) were quantified byflow cytometry. ATX expression was significantly enhanced inLPS or TMT treated BV2. LPS-induced CD11b, CD14, and B7.1and B7.2 were reduced in BV2A+. TNF and IL-6 were inhibitedin LPS or TMT treated BV2A+ while IL-10 level was increased.In vivo, elevated ATX mRNA levels in the hippocampus weredemonstrated in CD1 mice 5 days following an acute ip injectionof TMT (2 mg/kg bwt). With the pattern and time course ofresponse, our results suggest an involvement of ATX in regulat-ing microglia activation and neuroinflammation.
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R. Awada, S. Gres, J. S. Saulnier-Blache, G.Jean Harry, Christian Lefebvre d'Hellencourt. Anti-inflammatory effects of autotaxin on microglial cells. FEBS Journal, Wiley, 2011, 36th FEBS Congress, Biochemistry for Tomorrow's Medicine, Lingotto Conference Center, Torino, Italy, June 25‐30, 2011, 278, pp.266. ⟨10.1111/j.1742-4658.2011.08137.x⟩. ⟨hal-02309093⟩

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