کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5532742 1402072 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Crosstalk between glucocorticoids and IL-4 modulates Ym1 expression in alternatively activated myeloid cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Crosstalk between glucocorticoids and IL-4 modulates Ym1 expression in alternatively activated myeloid cells
چکیده انگلیسی

Airway epithelial cells induce a tolerogenic microenvironment by modulating immune cells in the lung. We recently showed that the supernatant of airway epithelial cells induces two marker genes of alternative activation, Ym1 and Ms4a8a, in respiratory myeloid cells. This induction was partially mediated by glucocorticoids, secreted by airway epithelial cells. In this study, we further investigated Ym1 and Ms4a8a regulation in alternatively activated myeloid cells in the presence of the TH2 cytokines IL-4 and IL-13. We show that Ym1 expression is boosted upon co-stimulation with airway epithelial cell supernatant and IL-4/IL-13, whereas Ms4a8a expression is down-regulated. This suggests that a crosstalk between IL-4/IL-13 and glucocorticoid signaling exists. Blocking protein synthesis indicated that dexamethasone-induced de novo protein synthesis is required for the interaction between glucocorticoid and IL-4 signaling regarding Ym1 regulation. Using reporter gene constructs, we demonstrate that the important regulatory region within the Ym1 promoter is found between −602 bp and −969 bp upstream of the start of translation. Bioinformatic analysis identified several glucocorticoid response elements (GREs) in this region. Further analysis identified overlapping but functionally active glucocorticoid receptor and STAT-6 binding sites, supporting the cooperative effect of glucocorticoids and IL-4 in the regulation of Ym1. These findings further prove the plasticity and complexity of alternatively activated myeloid cells and the importance of the local microenvironment. We believe that this regulation is of special importance in the pulmonary system, since both factors, glucocorticoids and IL-4/13, play a role in airway diseases such as asthma.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunobiology - Volume 222, Issue 5, May 2017, Pages 759-767
نویسندگان
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