Abstract
Previously, the authors reported that zaprinast, an inhibitor of cGMP-selective phosphodiesterases, induced the secretions of TNF-α and IL-1β by microglia and enhanced the induction of iNOS by lipopolysaccharide (LPS). In this study, the signaling mechanism responsible for microglial activation by zaprinast was investigated and the effects of zaprinast and LPS on microglial activation were compared. Zaprinast was found to activate ERK1/2, p38 MAPK, JNK, NFκB, and PI3K/Akt, and subsequently, induce the mRNA expressions of IL-1α, IL-1β, TNF-α, CCL2, CCL4, CXCL1, CXCL2, and CD14. Associations between signaling pathways and gene expressions were examined by treating microglia with signal inhibitors. PDTC inhibited the induction of all the above genes by zaprinast, and SB203580 inhibited all genes except CXCL1. SP600125, PD98059, and LY294002 inhibited the induction of at least CCL2. Microglial activation by zaprinast was then compared with full-blown activation by LPS. The zaprinast-induced phosphorylations of MAPKs and IκB were less prompt than LPS-induced phosphorylations. IκB degradation by LPS was significant at 10min and did not return to normal, whereas zaprinast induced a later, transient degradation. LPS induced the mRNA ex...Continue Reading
References
Mar 1, 1995·Brain Research. Brain Research Reviews·J GehrmannG W Kreutzberg
Jan 1, 1993·Agents and Actions·K Molnar-KimberB Weichman
Jan 1, 1993·The EMBO Journal·M NaumannC Scheidereit
Aug 1, 1996·Trends in Neurosciences·G W Kreutzberg
Sep 16, 1998·Current Opinion in Chemical Biology·M J Perry, G A Higgs
Jan 28, 1999·American Journal of Respiratory Cell and Molecular Biology·M FuhrmannN Suttorp
May 13, 1999·The Journal of Biological Chemistry·J D Corbin, S H Francis
Dec 22, 1999·Oncogene·H L Pahl
May 5, 2000·Biochemical Pharmacology·D M Essayan
Jan 4, 2001·European Journal of Pharmacology·A Gibson
Mar 21, 2001·Cellular Signalling·M Guha, N Mackman
Mar 22, 2001·The Journal of Biological Chemistry·L V MadridA S Baldwin
Oct 10, 2001·Journal of Neuroscience Research·Y LiW S Griffin
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·P M BauerL J Ignarro
Oct 12, 2001·Glia·F Aloisi
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·B L BennettD W Anderson
Jan 24, 2002·The Journal of Pharmacology and Experimental Therapeutics·John J HaddadRyszard Lauterbach
Oct 16, 2002·Glia·Milla Koistinaho, Jari Koistinaho
Oct 24, 2002·Cytokine·Anna M FiettaErnesto Pozzi
Sep 3, 2003·Nature Reviews. Drug Discovery·Sanjay KumarJohn C Lee
Jul 15, 2004·Current Opinion in Pharmacology·Jeremy Saklatvala
Sep 17, 2004·Journal of Neuroscience Research·Eleni DicouJean Mazella
Mar 2, 2005·Glia·Vicki WaetzigUwe-Karsten Hanisch
Apr 16, 2005·Science·Axel NimmerjahnFritjof Helmchen
Oct 4, 2005·Biochimica Et Biophysica Acta·Bozena Kaminska
Oct 26, 2005·Shock·Ben M TsaiDaniel R Meldrum
Apr 21, 2006·Immunological Reviews·Alexander Hoffmann, David Baltimore
Apr 4, 2007·Journal of Neurochemistry·Yan ZhouS Thameem Dheen
Aug 30, 2007·Cellular and Molecular Life Sciences : CMLS·Y Zhang, C Dong
Oct 30, 2007·Nature Neuroscience·Uwe-Karsten Hanisch, Helmut Kettenmann
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·R Bryan Rock, Phillip K Peterson
Nov 28, 2007·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Gwenn A Garden, Thomas Möller
Jan 1, 1992·Mediators of Inflammation·K L Molnar-KimberB M Weichman
Jul 29, 2008·International Journal of Cardiology·A M El-MowafyN N Nassar
Nov 28, 2009·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Bozena KaminskaMaciej Lipko
Dec 17, 2009·Journal of Neurochemistry·Paula PifarréAgustina Garcia
May 11, 2010·International Immunopharmacology·Hsiao-Yun LinDah-Yuu Lu
Nov 3, 2010·The Journal of Nutritional Biochemistry·Tsung-Kuei KaoChun-Jung Chen
Citations
Sep 26, 2015·Brain Research·Ana Karolina Santana NunesChristina Alves Peixoto
Jan 29, 2014·Neuropharmacology·Xiaoxiao WangJingyu Yang
Jun 29, 2016·International Immunopharmacology·Yuichiro TakaokaHiroshi Katsuki
Jan 21, 2016·PloS One·Chin Wai HuiKarl Herrup
May 7, 2019·Immunopharmacology and Immunotoxicology·Wonmin KoHyuncheol Oh
Jul 19, 2013·International Journal of Molecular Medicine·Shin Hwa LeeYung Hyun Choi
Dec 17, 2014·European Journal of Clinical Investigation·Susana Martin-RodriguezMaribel Diaz-Ricart
Oct 19, 2017·Journal of Experimental & Clinical Cancer Research : CR·Wei LiGuizhen Ao
Mar 11, 2017·Inflammopharmacology·Mahboobeh HajighorbaniAmin Hossein Amini
Nov 22, 2013·Pharmaceutical Biology·Jinglou ChenYongfang Lei
Oct 6, 2015·Biochemical and Biophysical Research Communications·Ji-Eun HamSang-Hyun Choi
May 13, 2021·Current Eye Research·Dan-Ning HuShun-Fa Yang