Glucocorticoid dexamethasone down-regulates basal and vitamin D3 induced cathelicidin expression in human monocytes and bronchial epithelial cell line.

To access publisher's full text version of this article click on the hyperlink at the bottom of the page 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 s...

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Bibliographic Details
Published in:Immunobiology
Main Authors: Kulkarni, Nikhil Nitin, Gunnarsson, Hörður Ingi, Yi, Zhiqian, Gudmundsdottir, Steinunn, Sigurjonsson, Olafur E, Agerberth, Birgitta, Gudmundsson, Gudmundur H
Other Authors: 1 Univ Iceland, Biomed Ctr, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland 2 Univ Iceland, Dept Life & Environm Sci, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland 3 Landspitali Univ Hosp, Blood Bank, Reykjavik, Iceland Organization-Enhanced Name(s) Landspitali National University Hospital 4 Reykjavik Univ, Inst Biomed & Neural Engn, Sch Sci & Engn, Reykjavik, Iceland 5 Univ Iceland, Biomed Ctr, Dept Anat, Fac Med,Sch Hlth Sci, IS-101 Reykjavik, Iceland 6 Karolinska Inst, Karolinska Univ Hosp, Div Clin Microbiol, Dept Lab Med, Stockholm, Sweden
Format: Article in Journal/Newspaper
Language:English
Published: Elsevier GMBH 2016
Subjects:
Bólgur
Meðferð
NAF12
Anti-Inflammatory Agents
Inflammation
Receptors
Glucocorticoid
Vitamin D3 24-Hydroxylase/genetics
Epithelial Cells
Gene Expression Regulation
Iceland
Online Access:http://hdl.handle.net/2336/606103
https://doi.org/10.1016/j.imbio.2015.09.001
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Summary:To access publisher's full text version of this article click on the hyperlink at the bottom of the page 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. Icelandic Centre for Research (RANNIS) 130202-052 University of Iceland Research Fund Swedish Foundation for Strategic Research (SSF) RBd08-0014 Swedish Heart-Lung Foundation 2013-0366 Swedish Research Council K2014-67X-11217-20-3 Wenner-Gren Foundation

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