High molecular weight hyaluronan reduces lipopolysaccharide mediated microglial activation

Journal of Neurochemistry
James W AustinMichael G Fehlings

Abstract

Toll-like receptor-4 (TLR4) signaling has been implicated in microglial activation and propagation of inflammation following spinal cord injury (SCI). As such, modulating microglial activation through TLR4 represents an attractive therapeutic approach to treat SCI. High molecular weight hyaluronan (HMW-HA), a polymer with multiple therapeutic uses, has been previously shown to modulate TLR4 activation in macrophages and has shown early promise as a therapeutic agent in SCI. However, the mechanism associated with HMW-HA has not been fully elucidated or tested in microglia, a similar cell type. In the current study, we sought to determine the effects of HMW-HA on TLR4 activation in microglia and to gain insights into the mechanism of action. Rat primary microglial cultures were exposed to lipopolysaccharides (LPS) and HMW-HA, and the extent and mechanisms of inflammation were studied. HMW-HA decreased LPS mediated IL-1β, IL-6, and Tumor necrosis factor-α gene expression and IL-6 and nitric oxide production. This decrease was associated with a reduction in ERK 1/2 and p38 phosphorylation, was dependent on the continued presence of HMW-HA, and activation of Akt and A20 protein expression was reduced by HMW-HA. Together, our results...Continue Reading

References

Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·J D SedgwickV ter Meulen
Apr 29, 1999·Proceedings of the National Academy of Sciences of the United States of America·J E Scott, F Heatley
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·K OhashiH Kolb
Jan 21, 2001·The Journal of Biological Chemistry·Y OkamuraJ F Strauss
Aug 18, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S T SmileyW W Hancock
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jun 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Seija LehnardtTimothy Vartanian
Sep 30, 2004·Journal of Neuropathology and Experimental Neurology·Weihua ZhaoStanley H Appel
Oct 7, 2004·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Monica J CarsonDavid Lo
Oct 26, 2005·Nature Medicine·Dianhua JiangPaul W Noble
Mar 2, 2006·Genome Biology·Christine A WellsSean M Grimmond
May 3, 2006·The American Journal of Pathology·Ilo JouEun Jung Park
Apr 4, 2007·Journal of Neurochemistry·Kristina A KigerlPhillip G Popovich
May 18, 2007·Annual Review of Cell and Developmental Biology·Dianhua JiangPaul W Noble
Jul 4, 2007·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·T Yasuda
Oct 4, 2007·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Zsuzsanna Pályi-KrekkPeter Nagy
Feb 29, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Vikas Kaushal, Lyanne C Schlichter
Mar 7, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Seija LehnardtJoerg R Weber
Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hidetada KawanaKenichi Harigaya
May 7, 2009·Journal of Neurochemistry·Christoph D SchmidMonica J Carson
Sep 25, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Erin G Reed-GeaghanGary E Landreth
Mar 9, 2010·The Tohoku Journal of Experimental Medicine·Tadashi Yasuda
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Huan YangKevin J Tracey
Aug 12, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Qing-Wu YangJing-Zhou Wang
Sep 30, 2010·Respirology : Official Journal of the Asian Pacific Society of Respirology·Pei-ming HuangCharles A Hales
Nov 30, 2010·Neuroscience Letters·Norimitsu WakaoKenji Kadomatsu
Jul 15, 2011·Journal of Neural Engineering·Zin Z KhaingChristine E Schmidt

❮ Previous
Next ❯

Citations

Jun 18, 2014·Regenerative Medicine·Fanwei MengStephen F Badylak
Jul 16, 2014·Experimental Neurology·Andrew D Gaudet, Phillip G Popovich
Jan 23, 2016·Cell Death and Differentiation·C ParisiC Volonté
Mar 5, 2016·Journal of Neurosurgery. Spine·Sergiy V KushchayevMark C Preul
Apr 15, 2014·Matrix Biology : Journal of the International Society for Matrix Biology·Mary Y ChangCharles W Frevert
Jan 30, 2014·Matrix Biology : Journal of the International Society for Matrix Biology·Mary Y ChangCharles W Frevert
Mar 20, 2013·Biomatter·Pouria Moshayedi, S Thomas Carmichael
Jan 24, 2018·Biomedical Materials·Agnes E HaggertyMartin Oudega
Dec 25, 2013·The Journal of Biological Chemistry·Milena SokolowskaJames H Shelhamer
Aug 23, 2020·International Journal of Molecular Sciences·Alec Peters, Larry S Sherman
Aug 14, 2019·International Journal of Molecular Sciences·Dmitry V ChistyakovMarina G Sergeeva
Oct 28, 2015·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zin Z Khaing, Stephanie K Seidlits
Dec 8, 2020·Frontiers in Cellular Neuroscience·María Lacalle-AuriolesThomas M Durcan
Dec 18, 2020·Frontiers in Cellular Neuroscience·Dieuwke Maria de Waard, Marianna Bugiani
Sep 15, 2020·Journal of Biomedical Materials Research. Part B, Applied Biomaterials·I-Ming JouYao-Lung Kuo
Apr 27, 2021·Frontiers in Cell and Developmental Biology·Laura N ZamproniMarimelia A Porcionatto
Oct 12, 2021·Ageing Research Reviews·Frances Tolibzoda ZakusiloVera Gorbunova

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here