کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2182767 1095514 2016 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glucocorticoid dexamethasone down-regulates basal and vitamin D3 induced cathelicidin expression in human monocytes and bronchial epithelial cell line
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Glucocorticoid dexamethasone down-regulates basal and vitamin D3 induced cathelicidin expression in human monocytes and bronchial epithelial cell line
چکیده انگلیسی


• Glucocorticoid (GC) dexamethasone down-regulates basal mRNA expression of the antimicrobial peptide genes CAMP (cathelicidin antimicrobial peptide), DEFB1 (human beta defensin 1), LZY (lysozyme) and SLPI (secretory leukocyte proteinase inhibitor 1) in THP-1 monocytes.
• Dexamethasone reduces vitamin D3 enhanced human cathelicidin (CAMP) gene expression in THP-1 monocytes, primary human monocytes and in the bronchial epithelial cell line BCi NS 1.1.
• The Glucocorticoid receptor inhibitor RU486 prevents dexamethasone mediated inhibition of CAMP gene.

Glucocorticoids (GCs) have been extensively used as the mainstream treatment for chronic inflammatory disorders. The persistent use of steroids in the past decades and the association with secondary infections warrants for detailed investigation into their effects on the innate immune system and the therapeutic outcome. In this study, we analyse the effect of GCs on antimicrobial polypeptide (AMP) expression. We hypothesize that GC related side effects, including secondary infections are a result of compromised innate immune responses. Here, we show that treatment with dexamethasone (Dex) inhibits basal mRNA expression of the following AMPs; human cathelicidin, human beta defensin 1, lysozyme and secretory leukocyte peptidase 1 in the THP-1 monocytic cell-line (THP-1 monocytes). Furthermore, pre-treatment with Dex inhibits vitamin D3 induced cathelicidin expression in THP-1 monocytes, primary monocytes and in the human bronchial epithelial cell line BCi NS 1.1. We also demonstrate that treatment with the glucocorticoid receptor (GR) inhibitor RU486 counteracts Dex mediated down-regulation of basal and vitamin D3 induced cathelicidin expression in THP-1 monocytes. Moreover, we confirmed the anti-inflammatory effect of Dex. Pre-treatment with Dex inhibits dsRNA mimic poly IC induction of the inflammatory chemokine IP10 (CXCL10) and cytokine IL1B mRNA expression in THP-1 monocytes. These results suggest that GCs inhibit innate immune responses, in addition to exerting beneficial anti-inflammatory effects.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunobiology - Volume 221, Issue 2, February 2016, Pages 245–252
نویسندگان
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