Laquinimod Modulates Human Astrocyte Function and Dampens Astrocyte-Induced Neurotoxicity during Inflammation.

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Emanuela ColomboCinthia Farina

Abstract

Astrocytes greatly participate to inflammatory and neurotoxic reactions occurring in neurodegenerative diseases and are valuable pharmacological targets to support neuroprotection. Here we used human astrocytes generated from reprogrammed fibroblasts as a cellular model to study the effect of the compound Laquinimod and its active metabolite de-Laquinimod on astrocyte functions and the astrocyte-neuron interaction. We show that human iAstrocytes expressed the receptor for the inflammatory mediator IL1 and responded to it via nuclear translocation of NFκB, an event that did not occur if cells were treated with Laquinimod, indicating a direct anti-inflammatory activity of the drug on the human astrocyte. Similarly, while exposure to IL1 downregulated glial glutamate transporters GLAST and GLT1, treatment with Laquinimod supported maintenance of physiological levels of these proteins despite the inflammatory milieu. Laquinimod also induced nuclear translocation of the aryl hydrocarbon receptor (AHR), suggesting that drug action was mediated by activation of the AHR pathway. However, the drug was effective despite AHR inhibition via CH223191, indicating that AHR signaling in the astrocyte is dispensable for drug responses. Finally,...Continue Reading

References

Jun 8, 2001·The American Journal of Pathology·J S LiuS C Lee
Apr 19, 2002·Journal of Neuroimmunology·Makoto OhgohYukio Nishizawa
Jun 3, 2004·Life Sciences·Fugen Aktan
Mar 15, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Helén TuvessonJaneric Seidegård
Feb 6, 2007·Trends in Immunology·Cinthia FarinaEdgar Meinl
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Roberta BrambillaJohn R Bethea
Mar 31, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xiangyu MaHongwei Qin
Jul 17, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Bin ZhaoMichael S Denison
Mar 25, 2011·Journal of the Neurological Sciences·W Brück, C Wegner
Jan 5, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Melissa CambronJacques De Keyser
Mar 7, 2012·The Journal of Experimental Medicine·Emanuela ColomboCinthia Farina
Mar 16, 2012·The New England Journal of Medicine·Giancarlo ComiUNKNOWN ALLEGRO Study Group
Jul 4, 2012·The American Journal of Pathology·Manoj K MishraV Wee Yong
Jul 7, 2012·Acta Neuropathologica·Wolfgang BrückChristiane Wegner
Dec 13, 2012·Multiple Sclerosis : Clinical and Laboratory Research·Francesca RuffiniGianvito Martino
Mar 23, 2013·Brain : a Journal of Neurology·Valérie JolivelAri Waisman
Sep 14, 2013·Journal of Neurology, Neurosurgery, and Psychiatry·Massimo FilippiUNKNOWN ALLEGRO Study Group
Feb 14, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Iain L CampbellJuan Hidalgo
Feb 19, 2014·Journal of Neurology·T L VollmerUNKNOWN BRAVO Study Group
Jul 22, 2014·Annals of Neurology·Emanuela ColomboCinthia Farina
Oct 31, 2014·Annals of Clinical and Translational Neurology·Manoj Kumar MishraV Wee Yong
Nov 9, 2014·Cold Spring Harbor Perspectives in Biology·Michael V Sofroniew
May 20, 2016·Brain Sciences·Maria ErtaJuan Hidalgo
May 28, 2016·Neurology. Neuroimmunology and Neuroinflammation·Nadine KramannWolfgang Brück
Jul 23, 2016·Trends in Immunology·Emanuela Colombo, Cinthia Farina
Sep 28, 2016·Proceedings of the National Academy of Sciences of the United States of America·Joel KayeRalph Laufer
Feb 6, 2017·Journal of Neuroscience Research·Ciaran Murphy-RoyalStéphane H R Oliet
Jun 16, 2017·The Journal of Biological Chemistry·Michael A WheelerFrancisco J Quintana
Jul 12, 2017·Scientific Reports·Gisa EllrichmannRalf Gold
Nov 22, 2017·Signal Transduction and Targeted Therapy·Ting LiuShao-Cong Sun
Jan 7, 2018·Journal of Neuroinflammation·Antonietta GentileGeorgia Mandolesi
Dec 6, 2018·International Journal of Molecular Sciences·Drew R NeavinRichard M Weinshilboum
Feb 6, 2019·Nature Reviews. Immunology·Veit Rothhammer, Francisco J Quintana
Jan 25, 2020·Nature Communications·Emily E BurkeAndrew E Jaffe

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Methods Mentioned

BETA
nuclear translocation
biopsies
FCS

Software Mentioned

LASX
Excel
ImageJ
GraphPad Prism

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