Vitamin D Modulates the Response of Bronchial Epithelial Cells Exposed to Cigarette Smoke Extract.

Carolien Mathyssen,Bart Vanaudenaerde,Ghislaine Gayan-Ramirez,Lieve Verlinden,Charles Pilette,Jef Serré,Stephanie Everaerts,Annelore Sacreas,Annemieke Verstuyf,Karen Maes,Stijn Verleden,Wim Janssens

doi:10.3390/nu11092138

Carolien Mathyssen, Bart Vanaudenaerde + Show 10 more

Open Access

https://doi.org/10.3390/nu11092138

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Journal: Nutrients	Publication Date: Sep 6, 2019
Citations: 14	License type: CC BY 4.0

Affiliation: KU Leuven, Université Catholique de Louvain

Abstract

In chronic obstructive pulmonary disease (COPD), the bronchial epithelium is the first immune barrier that is triggered by cigarette smoke. Although vitamin D (vitD) has proven anti-inflammatory and antimicrobial effects in alveolar macrophages, little is known about the direct role of vitD on cigarette smoke-exposed bronchial epithelial cells. We examined the effects of vitD on a human bronchial epithelial cell line (16HBE) and on air–liquid culture of primary bronchial epithelial cells (PBEC) of COPD patients and controls exposed for 24 h to cigarette smoke extract (CSE). VitD decreased CSE-induced IL-8 secretion by 16HBE cells, but not by PBEC. VitD significantly increased the expression of the antimicrobial peptide cathelicidin in 16HBE and PBEC of both COPD subjects and controls. VitD did not affect epithelial to mesenchymal transition or epithelial MMP-9 expression and was not able to restore impaired wound healing by CSE in 16HBE cells. VitD increased the expression of its own catabolic enzyme CYP24A1 thereby maintaining its negative feedback. In conclusion, vitD supplementation may potentially reduce infectious exacerbations in COPD by the upregulation of cathelicidin in the bronchial epithelium.

Highlights

Cigarette smoking is the major risk factor for the development of chronic obstructive pulmonary disease (COPD) [1]
We found that vitamin D (vitD) was able to upregulate cathelicidin in both cell-line and primary cell cultures, but downregulation of cigarette smoke extract (CSE)-induced IL-8 production was only seen in the 16HBE cell-line and not in primary bronchial epithelial cells (PBEC)
We demonstrate the anti-microbial potential of vitamin D (1,25(OH)2 D and 25(OH)D) and of the vitD analogue TX527 on airway epithelial cells by the upregulation of the antimicrobial peptide cathelicidin

Summary

Introduction

Cigarette smoking is the major risk factor for the development of chronic obstructive pulmonary disease (COPD) [1]. The bronchial epithelium is the first barrier encountered by harmful triggers such as cigarette smoke and infections. The epithelium operates as a physical and chemical barrier and may, by releasing reactive oxygen species and antimicrobial peptides, prevent particles and pathogens from invading the lung [2]. When pathogens invade the lung, a cellular response of neutrophils and macrophages is induced together with the production and release of cytokines and chemokines [3,4]. COPD is characterized by a decreased wound healing and a progressive airway remodeling in which matrix metalloproteases, especially MMP-9 play an important part [5,6].

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