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Although previous reports investigated TLR signaling in response to intact H. pylori, the specific contribution of H. pylori LPS with regard to functional genomics and cell-signaling events has not been defined. This study set out to define downstream signaling components and altered gene expression triggered by H. pylori LPS and to investigate the role of the signaling protein tribbles 3 (TRIB3) during the TLR-mediated response to H. pylori LPS. Cotransfections using small interfering RNA and dominant-negative constructs demonstrated that H. pylori LPS functions as a classic TLR2 ligand by signaling through pathways involving the key TLR signaling components MyD88 adaptor-like, MyD88, IRAK1, IRAK4, TNFR-associated factor 6, I\u03baB kinase \u03b2, and I\u03baB\u03b1. Microarray analysis, real-time PCR, and ELISA revealed the induction of a discrete pattern of chemokines as a direct effect of LPS:TLR2 signaling. H. pylori infection was associated with decreased expression of TRIB3 in human gastric epithelial cell lines and tissue samples. Additionally, H. pylori decreased expression of C\/EBP homologous protein and activating transcription factor 4, the transcription factors involved in the induction of TRIB3 expression. Furthermore, knockdown of TRIB3 and C\/EBP homologous protein enhanced TLR2-mediated NF-\u03baB activation and chemokine induction in response to H. pylori LPS. Thus, modulation of TRIB3 by H. pylori and\/or its products may be an important mechanism during H. pylori-associated pathogenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.1000864","type":"journal-article","created":{"date-parts":[[2011,1,10]],"date-time":"2011-01-10T22:41:38Z","timestamp":1294699298000},"page":"2462-2471","source":"Crossref","is-referenced-by-count":66,"title":["Tribbles 3: A Novel Regulator of TLR2-Mediated Signaling in Response to\n                    <i>Helicobacter pylori<\/i>\n                    Lipopolysaccharide"],"prefix":"10.1093","volume":"186","author":[{"given":"Sin\u00e9ad M","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine, Trinity College Dublin , Dublin 8 ,","place":["Ireland"]},{"name":"Immunology Research Centre, Trinity College Dublin , Dublin 2 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony P","family":"Moran","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Natural Sciences, National University of Ireland , Galway ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane P","family":"Duggan","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Trinity College Dublin , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salah E","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St. James\u2019s Hospital , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelhafeez S","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, St. James\u2019s Hospital , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J","family":"Windle","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Trinity College Dublin , Dublin 8 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"Immunology Research Centre, Trinity College Dublin , Dublin 2 ,","place":["Ireland"]},{"name":"Department of Biochemistry and Immunology, Trinity College Dublin , Dublin 2 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dermot P","family":"Kelleher","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Trinity College Dublin , Dublin 8 ,","place":["Ireland"]},{"name":"Immunology Research Centre, Trinity College Dublin , Dublin 2 ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,2,15]]},"reference":[{"key":"2025032411044679100_r1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1128\/CMR.00054-05","article-title":"Pathogenesis of Helicobacter pylori infection","volume":"19","author":"Kusters","year":"2006","journal-title":"Clin. 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