کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9245494 | 1209948 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Clostridium difficile toxin B activates the EGF receptor and the ERK/MAP kinase pathway in human colonocytes
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کلمات کلیدی
PTXTXBTXATgf-αIL-8EGFRPKCGPCRERKSDSMMPDMSO - DMSOG-protein-coupled receptor - G-پروتئین گیرندهNFκB - NFKBInterleukin 8 - اینترلوکین 8transforming growth factor α - تبدیل عامل فاکتور αToxin A - توکسین Atoxin B - توکسین BDimethyl sulfoxide - دیمتیل سولفواکسیدsodium dodecyl sulfate - سدیم دودسیل سولفاتpertussis toxin - سموم سورافنیNuclear factor κ B - عامل هسته ای κ BMetalloproteinase - متالوپروتئیناز map - نقشهmitogen-activated protein - پروتئین فعال mitogenProtein kinase C - پروتئین کیناز سیextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Clostridium difficile toxin B activates the EGF receptor and the ERK/MAP kinase pathway in human colonocytes Clostridium difficile toxin B activates the EGF receptor and the ERK/MAP kinase pathway in human colonocytes](/preview/png/9245494.png)
چکیده انگلیسی
Background & Aims: Clostridium difficile toxin B (TxB) mediates acute inflammatory diarrhea characterized by neutrophil infiltration and intestinal mucosal injury. In a xenograft animal model, TxB was shown to induce interleukin (IL)-8 gene expression in human colonic epithelium. However, the precise mechanisms of this TxB response are unknown. The aim of this study was to investigate the TxB-mediated proinflammatory pathway in colonocytes. Methods: The effect of TxB on epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) 1/2 signaling pathway and IL-8 gene expression was assessed in nontransformed human colonic epithelial NCM460 cells. TxB regulation of EGFR-ERK1/2 signaling pathways was determined using immunoblot analysis, confocal microscopy, and enzyme-linked immunosorbent assay, whereas IL-8 gene expression was measured by luciferase promoter assay. Results: TxB activates EGFR and ERK1/2 phosphorylation with subsequent release of IL-8 from human colonocytes. Pretreatment with either the EGFR tyrosine kinase inhibitor, AG1478, or an EGFR-neutralizing antibody blocked both TxB-induced EGFR and ERK activation. By using neutralizing antibodies against known ligands of EGFR, we found that the activation of EGFR and ERK1/2 phosphorylation was mediated by transforming growth factor-α (TGF-α). Inhibition of matrix metalloproteinase (MMP) decreased TGF-α secretion and TxB-induced EGFR and ERK activation. Inhibition of MMP, EGFR, and ERK activation significantly decreased TxB-induced IL-8 expression. Conclusions: TxB signals acute proinflammatory responses in colonocytes by transactivation of the EGFR and activation of the ERK/MAP kinase pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 128, Issue 4, April 2005, Pages 1002-1011
Journal: Gastroenterology - Volume 128, Issue 4, April 2005, Pages 1002-1011
نویسندگان
Xi Na, Dezheng Zhao, Hon Wai Koon, Ho Kim, Johanna Husmark, Mary P. Moyer, Charalabos Pothoulakis, J. Thomas Lamont,