کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2535063 1559109 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Transcriptional down-regulation of human α2A-adrenoceptors by IFNγ and TNFα in intestinal cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Transcriptional down-regulation of human α2A-adrenoceptors by IFNγ and TNFα in intestinal cells
چکیده انگلیسی

α2A-adrenoceptors are expressed on intestinal cells and they participate in the control of epithelial functions such as solute and water transport or cell proliferation. In pathological conditions, pro-inflammatory cytokines secreted by lymphocytes are responsible for modification of intestinal cell characteristics including phenotype switch and changes in the expression of pumps and ion channels. Using the HT29 cell line as a model, the present work examined the effect of two inflammatory cytokines, interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα), on the expression of the human α2A-adrenoceptor. Exposure of cells to either IFNγ or TNFα resulted in a concentration- and time-dependent diminution of [3H]RX821002 binding sites, which is preceded by a large decrease in the amount of α2A-adrenoceptor mRNA. The cytokines did not affect the receptor mRNA half-life, but inhibited the activity of a luciferase construct containing the promoter region of α2A-adrenoceptor gene, indicating that a decrease in the transcription rate is primarily responsible for the diminution of receptor expression. Exposure of cells to either IFNγ or TNFα caused increased production of reactive oxygen species and transient phosphorylation of extracellular signal-regulated kinase (Erk1/2). The effect of cytokines was mimicked by H2O2 but was unaffected by the addition of anti-oxidants. The blockade of Erk1/2 activation by PD98059 blunted the effect of TNFα but not of IFNγ. In conclusion, the present findings demonstrate that IFNγ and TNFα diminish the α2A-adrenoceptor expression in HT29 cells by decreasing the transcription rate without modifying the stability of mRNA. The transcription inhibition is however triggered via different signalling pathways. The results suggest that cytokine-mediated down-regulation of α2A-adrenoceptor could contribute to the pathogenesis of inflammatory bowel disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 588, Issue 1, 24 June 2008, Pages 33–40
نویسندگان
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