کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2775459 1152327 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Small molecule inhibitors of the host cell COX/AREG/EGFR/ERK pathway attenuate cytomegalovirus-induced pathogenesis
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی بالینی
پیش نمایش صفحه اول مقاله
Small molecule inhibitors of the host cell COX/AREG/EGFR/ERK pathway attenuate cytomegalovirus-induced pathogenesis
چکیده انگلیسی

As with other herpesviruses, human cytomegalovirus (hCMV) has the ability to establish lifelong persistence and latent infection following primary exposure, salivary glands (SMGs) being the primary site of both. In the immunocompromised patient, hCMV is a common cause of opportunistic infections, and subsequent morbidity and mortality. Elucidating the molecular pathogenesis of CMV-induced disease is critical to the development of more effective and safer drug therapies. In the present study, we used a novel mouse postnatal SMG organ culture model of mCMV-induced dysplasia to investigate a candidate signaling network suggested by our prior studies (COX-2/AREG/EGFR/ERK). The objective was to employ small molecule inhibitors to target several key steps in the autocrine loop, and in this way ameliorate pathology. Our results indicate that upregulation of ERK phosphorylation is necessary for initial mCMV-induced pathogenesis, and that ErbB receptor family phosphorylation and downstream signaling are highly relevant targets for drug discovery.

Research highlights
► CMV-induced pathology is mediated by the COX-2/AREG/EGFR/ERK autocrine loop.
► Small molecule inhibitors of several key pathway members greatly attenuate pathology.
► Upregulation of pERK is necessary for initial CMV-induced pathogenesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental and Molecular Pathology - Volume 91, Issue 1, August 2011, Pages 400–410
نویسندگان
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