Abstract
Both NOD2/CARD15 alleles are mutated in approximately 10% of Crohn's disease patients, causing loss of functional responses to low-dose muropeptide agonists. We hypothesized that NOD2 mutations may also impair NOD1/CARD4 responses, supported by data suggesting NOD2 1007fs/1007fs patients had reduced responses to a putative NOD1 agonist, diaminopimelic acid-containing muramyl tripeptide (M-TriDAP). We measured peripheral blood mononuclear cell (n = 8 NOD2 wild type, n = 4 1007fs/1007fs, n = 6 702Trp/1007fs, n = 5 702Trp/702Trp, n = 3 908Arg/1007fs) responses to NOD1 agonists alone (IL-8/TNF-alpha), and agonist enhancement of lipopolysaccharide (LPS) responses (IL-1beta). Significant responses were seen with M-TriDAP at 10 nM (as with NOD2 agonists), but only at > or =100 nM with FK565/TriDAP. M-TriDAP induced IL-8/TNF-alpha secretion, and enhancement of LPS IL-1beta responses was significantly reduced between NOD2 double mutation carriers versus healthy controls, whereas there was no difference with FK565 or TriDAP stimulation, or between 1007fs/1007fs cells and other genotypes. M-TriDAP contains both NOD1 (gamma-D-Glu-mesoDAP) and NOD2 (MurNAc-L-Ala-D-Glu) minimal structures whereas FK565/TriDAP contain only NOD1 activating str...Continue Reading
References
Nov 1, 1984·Infection and Immunity·M W Vermeulen, G R Gray
Apr 1, 1982·Journal of Medicinal Chemistry·Y KitauraM Hashimoto
Jul 6, 2000·The Journal of Biological Chemistry·N InoharaG Núñez
Nov 4, 2000·The Journal of Biological Chemistry·N InoharaG Nuñez
Jun 1, 2001·Nature·J P HugotG Thomas
Jun 1, 2001·Nature·Y OguraJ H Cho
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Jan 7, 2003·The Journal of Biological Chemistry·Naohiro InoharaGabriel Nuñez
Jun 7, 2003·Science·Stephen E GirardinDana J Philpott
Jun 11, 2003·Nature Immunology·Mathias ChamaillardNaohiro Inohara
Jul 23, 2003·The Journal of Biological Chemistry·Stephen E GirardinDominique Mengin-Lecreulx
Apr 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Apr 27, 2004·The Biochemical Journal·Jason S DamianoJohn C Reed
Jun 17, 2004·Human Molecular Genetics·Jing LiJudy H Cho
Sep 14, 2004·Oncogene·Jerry UsaryCharles M Perou
Nov 3, 2004·Gastroenterology·Stephan R VavrickaEugene B Chang
Dec 25, 2004·Cellular Microbiology·A UeharaH Takada
Dec 29, 2004·Current Biology : CB·Derek W AbbottLewis C Cantley
Dec 30, 2004·Physiological Genomics·Tatiana K ZagranichnayaMitchel L Villereal
May 25, 2005·Lancet·David A van HeelRaymond J Playford
Jun 2, 2005·Gut·D A van HeelR J Playford
Jul 7, 2005·The Journal of Cell Biology·Nicolas BarnichDaniel K Podolsky
Jul 16, 2005·European Journal of Immunology·Jörg H FritzMinou Adib-Conquy
Jul 16, 2005·European Journal of Immunology·David A van HeelRaymond J Playford
Aug 24, 2005·The Journal of Biological Chemistry·Mihai G NeteaStephen E Girardin
Jan 19, 2006·The Journal of Experimental Medicine·Junya MasumotoNaohiro Inohara
Dec 8, 2006·Nucleic Acids Symposium Series·Hiroyasu InoharaTakeshi Imanishi
Citations
Jan 9, 2007·Inflammatory Bowel Diseases·Johan Van LimbergenJack Satsangi
Sep 21, 2013·European Journal of Medicinal Chemistry·Žiga JakopinMarija Sollner Dolenc
Jul 16, 2011·The Journal of Biological Chemistry·Hamed LarouiDidier Merlin
Jan 20, 2007·American Journal of Respiratory and Critical Care Medicine·Neil CartwrightJane A Mitchell
Aug 12, 2016·PloS One·Yulia A DagilMikhail V Pashenkov
Aug 30, 2014·Inflammatory Bowel Diseases·Tracy CoelhoSarah Ennis
Oct 3, 2006·European Journal of Immunology·Gerben FerwerdaMihai G Netea
Mar 1, 2012·Natural Product Reports·Yukari FujimotoKoichi Fukase
Feb 4, 2009·The FEBS Journal·Li LiuKiyoshi Fukui
Nov 27, 2007·Annals of Medicine·Leticia A M CarneiroStephen E Girardin
Apr 9, 2014·Journal of Medicinal Chemistry·Žiga Jakopin