Nanog attenuates lipopolysaccharide-induced inflammatory responses by blocking nuclear factor-&kgr;B transcriptional activity in BV-2 cells

Nanog, a unique homeobox transcription factor, maintains self-renewal and pluripotency of embryonic stem cells by binding to nuclear factor &kgr;B proteins in order to inhibit their transcriptional and prodifferentiation activities. We previously reported that Nanog attenuated inflammatory responses in rat primary microglia cells stimulated by lipopolysaccharide. However, the effects of Nanog on another microglia cell type, BV-2 cells, are still unknown. In this study, we investigated whether Nanog attenuated inflammatory responses in lipopolysaccharide-stimulated BV-2 cells and found that Nanog significantly decreased the release of nitric oxide and the expression of inducible nitric oxide synthase at the mRNA and protein levels. The production of proinflammatory cytokines including tumor necrosis factor-&agr; and interleukin-1&bgr; was also significantly inhibited by Nanog. Further, we observed that the transcriptional activity of nuclear factor &kgr;B was dramatically reduced by Nanog. These results suggest that Nanog may be a potential anti-inflammatory therapy for neurological diseases caused by persistent microglia activation.

[1]  Zhijian J. Chen,et al.  Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway , 2013, Science.

[2]  Y. Liu,et al.  Adenosine A2a receptor induces GDNF expression by the Stat3 signal in vitro , 2012, Neuroreport.

[3]  C. Casteleyn,et al.  Interferon-&ggr; modulates the functional profile of in-vitro-cultured porcine microglia , 2012, Neuroreport.

[4]  M. Yaster,et al.  Absence of &mgr; opioid receptor mRNA expression in astrocytes and microglia of rat spinal cord , 2012, Neuroreport.

[5]  Xiuli Wu,et al.  Nanog inhibits lipopolysaccharide-induced expression of pro-inflammatory cytokines by blocking NF-κB transcriptional activity in rat primary microglial cells. , 2011, Molecular medicine reports.

[6]  Y. Lee,et al.  Vascular Protective Role of Vitexicarpin Isolated from Vitex rotundifolia in Human Umbilical Vein Endothelial Cells , 2011, Inflammation.

[7]  Xian Wang,et al.  Nuclear factor-&kgr;B is involved in the phenotype loss of parvalbumin-interneurons in vitro , 2011, Neuroreport.

[8]  Woong Sun,et al.  Induction of ezrin–radixin–moesin molecules after cryogenic traumatic brain injury of the mouse cortex , 2011, Neuroreport.

[9]  J. Shen,et al.  NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation , 2011, Oncogene.

[10]  Eunjung Moon,et al.  Chrysin suppresses LPS-stimulated proinflammatory responses by blocking NF-κB and JNK activations in microglia cells , 2010, Neuroscience Letters.

[11]  M. Lako,et al.  Opposing Putative Roles for Canonical and Noncanonical NFκB Signaling on the Survival, Proliferation, and Differentiation Potential of Human Embryonic Stem Cells , 2010, Stem cells.

[12]  Seung Ho Lee,et al.  Pinoresinol from the fruits of Forsythia koreana inhibits inflammatory responses in LPS-activated microglia , 2010, Neuroscience Letters.

[13]  P. Agostinho,et al.  Neuroinflammation, oxidative stress and the pathogenesis of Alzheimer's disease. , 2010, Current pharmaceutical design.

[14]  Guy C. Brown,et al.  Inflammatory Neurodegeneration and Mechanisms of Microglial Killing of Neurons , 2010, Molecular Neurobiology.

[15]  K. Kaestner,et al.  KLF Family Members Regulate Intrinsic Axon Regeneration Ability , 2009, Science.

[16]  Ge Guo,et al.  Nanog Is the Gateway to the Pluripotent Ground State , 2009, Cell.

[17]  Fiona M. Watt,et al.  Nanog maintains pluripotency of mouse embryonic stem cells by inhibiting NFκB and cooperating with Stat3 , 2008, Nature Cell Biology.

[18]  T. Möller,et al.  Microglia Biology in Health and Disease , 2006, Journal of Neuroimmune Pharmacology.

[19]  M. Murakami,et al.  The Homeoprotein Nanog Is Required for Maintenance of Pluripotency in Mouse Epiblast and ES Cells , 2003, Cell.

[20]  J. Nichols,et al.  Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem Cells , 2003, Cell.

[21]  M. Block,et al.  Microglia-mediated neurotoxicity: uncovering the molecular mechanisms , 2007, Nature Reviews Neuroscience.

[22]  C. Kaltschmidt,et al.  Potential role of NF-kappaB in adult neural stem cells: the underrated steersman? , 2006, International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience.

[23]  Xiao-Min Wang,et al.  Triptolide inhibits TNF-alpha, IL-1 beta and NO production in primary microglial cultures. , 2003, Neuroreport.