Abstract
Lipoxins have emerged as mediators of key events in endogenous anti-inflammation and resolution. However, the implication of these novel lipid mediators on neuroinflammation has not been investigated. Microglia is the major cells involved in brain tissue damage during infection and neurodegenerative diseases. One of the major features shared by neuroinflammation conditions is the increased production of reactive oxygen species (ROS) generated by NADPH oxidase activation. In this study, we have examined whether aspirin-triggered lipoxin A4 (ATL) modulates ROS generation in BV2 cells. Pre-treatment of BV2 cells with ATL blocked ROS production triggered by LPS in the time-dependent and concentration-dependent manner. ATL inhibited the translocation of the cytoplasmic NADPH oxidase subunit p47phox to the cell membrane as well as NADPH oxidase activity. Taken together, these results demonstrate that ATL suppresses NADPH oxidase-mediated ROS generation in BV2 microglia cells, strongly indicating that ATL may play an important role against the development and progression of neuroinflammtion.
References
Finkel T (1999) Signal transduction by reactive oxygen species in non-phagocytic cells. J Leukoc Biol 65:337–340
Maulik N (2002) Redox signaling of angiogenesis. Antioxid Redox Signal 4:805–815
Floyd RA (1999) Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 222:236–245
Block ML, Hong JS (2007) Chronic microglial activation and progressive dopaminergic neurotoxicity. Biochem Soc Trans 35:1127–1132
Clària J, Serhan CN (1995) Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. Proc Natl Acad Sci USA 92:9475–9479
Chiang N, Arita M, Serhan CN (2005) Anti-inflammatory circultry: lipoxin, aspirin- triggered lipoxins and their receptor ALX. Prostaglandins Leukot Essent Fat Acids 73:163–177
Maddox JF, Hachicha M, Takano T et al (1997) Lipoxin A4 stable analogues are potent mimetics that stimulate human monocytes and THP-1 cell via a G-protein linked lipoxin A4 receptor. J Biol Chem 272:6972–6978
Sodin-Semrl S, Spagnolo A, Mikus R et al (2004) Opposing regulation of interleukin-8 and NF-kappaB responses by lipoxinA4 and serumamyloid Avia the common lipoxin A receptor. Int J Immunopathol Pharmacol 17:145–156
Wada K, Arita M, Nakajima A et al (2006) Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation. FASEB J 20:1785–1792
Svensson CI, Zattoni M, Serhan CN (2007) Lipoxins and aspirin triggered lipoxin inhibit inflammatory pain processing. J Exp Med 204:245–252
Wu Y, Ye XH, Guo PP et al (2010) Neuroprotective effect of lipoxin A(4) methyl ester in a rat model of permanent focal cerebral ischemia. J Mol Neurosci 42: 226–234
Ye XH, Wu Y, Guo PP et al (2010) Lipoxin A4 analogue protects brain and reduces inflammation in a rat model of focal cerebral ischemia reperfusion. Brain Res 1323:174–183
Wu Y, Wang YP, Guo P et al (2011) A Lipoxin A(4) analog ameliorates blood-brain barrier dysfunction and reduces MMP-9 expression in a rat Model of focal cerebral ischemia-reperfusion injury. J Mol Neurosci 46(3):483–491
Wang YP, Wu Y, Li LY et al (2011) Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells. J Neuroinflammation 8:95
Wu Y, Shang Y, Sun S et al (2007) Antioxidant effect of erythropoietin on 1-methyl-4-phenylpyridinium-induced neurotoxicity in PC12 cells. Eur J Pharmacol 564:47–56
Liva SM, Kahn MA, Dopp JM et al (1999) Signal transduction pathways induced by GM-CSF in microglia: significance in the control of proliferation. Glia 26:344–352
Emerit J, Edeas M, Bricaire F (2004) Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 58:39–46
Wang JY, Wen LL, Huang YN et al (2006) Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation. Curr Pharm Des 12:3521–3533
Börgeson E, Lönn J, Bergström I et al (2011) Lipoxin A4 inhibits porphyromonas gingivalis-induced aggregation and reactive oxygen species production by modulating neutrophil-platelet interaction and CD11b expression. Infect Immun 79:1489–1497
Nascimento-Silva V, Arruda MA, Barja-Fidalgo C et al (2007) Aspirin-triggered lipoxin A4 blocks reactive oxygen species generation in endothelial cells: a novel antioxidative mechanism. Thromb Haemost 97:88–98
Qin L, Liu Y, Wang T et al (2004) NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J Biol Chem 279:1415–1421
Groemping Y, Rittinger K (2005) Activation and assembly of the NADPH oxidase: a structural perspective. Biochem J 386:401–416
Acknowledgments
This study was supported Natural Science Foundation of China (No.30900448, No.30700784) and Excellent Youth Scholars Foundation of Education Ministry of China. (NO.20090142120047).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Wu, Y., Zhai, H., Wang, Y. et al. Aspirin-Triggered Lipoxin A4 Attenuates Lipopolysaccharide-Induced Intracellular ROS in BV2 Microglia Cells by Inhibiting the Function of NADPH Oxidase. Neurochem Res 37, 1690–1696 (2012). https://doi.org/10.1007/s11064-012-0776-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-012-0776-3