{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:35:14Z","timestamp":1774125314146,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,4,24]],"date-time":"2006-04-24T00:00:00Z","timestamp":1145836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Both NOD2\/CARD15 alleles are mutated in \u223c10% of Crohn's disease patients, causing loss of functional responses to low\u2010dose 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\u2010containing muramyl tripeptide (M\u2010TriDAP). We measured peripheral blood mononuclear cell (<jats:italic>n<\/jats:italic> = 8 NOD2 wild type, <jats:italic>n<\/jats:italic> = 4 1007fs\/1007fs, <jats:italic>n<\/jats:italic> = 6 702Trp\/1007fs, <jats:italic>n<\/jats:italic> = 5 702Trp\/702Trp, <jats:italic>n<\/jats:italic> = 3 908Arg\/1007fs) responses to NOD1 agonists alone (IL\u20108\/TNF\u2010\u03b1), and agonist enhancement of lipopolysaccharide (LPS) responses (IL\u20101\u03b2). Significant responses were seen with M\u2010TriDAP at 10\u2004nM (as with NOD2 agonists), but only at \u2a7e100\u2004nM with FK565\/TriDAP. M\u2010TriDAP induced IL\u20108\/TNF\u2010\u03b1 secretion, and enhancement of LPS IL\u20101\u03b2 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\u2010TriDAP contains both NOD1 (\u03b3\u2010D\u2010Glu\u2010mesoDAP) and NOD2 (MurNAc\u2010L\u2010Ala\u2010D\u2010Glu) minimal structures whereas FK565\/TriDAP contain only NOD1 activating structures. M\u2010TriDAP has dual NOD1\/NOD2 agonist activity in primary cells, possibly due to different intracellular peptidoglycan processing compared to the HEK293 cell system typically used for agonist specificity studies. Responses to specific NOD1 agonists are unaffected by NOD2 genotype, suggesting independent action of the NOD1 and NOD2 pathways.<\/jats:p>","DOI":"10.1002\/eji.200535636","type":"journal-article","created":{"date-parts":[[2006,4,24]],"date-time":"2006-04-24T16:55:04Z","timestamp":1145897704000},"page":"1629-1635","source":"Crossref","is-referenced-by-count":14,"title":["Normal responses to specific NOD1\u2010activating peptidoglycan agonists in the presence of the NOD2 frameshift and other mutations in Crohn's disease"],"prefix":"10.1002","volume":"36","author":[{"given":"David\u2004A.","family":"van Heel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen\u2004A.","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subrata","family":"Ghosh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireille","family":"Herv\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond\u2004J.","family":"Playford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,5,24]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200673200"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni945"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084677"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307198200"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.12.032"},{"key":"e_1_2_7_6_2","doi-asserted-by":"crossref","first-page":"27823","DOI":"10.1074\/jbc.M003415200","article-title":"An induced proximity model for NF\u2010kappa B activation in the Nod1\/RICK and RIP signalling pathways.","volume":"275","author":"Inohara N.","year":"2000","journal-title":"J. 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