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Sinusitis 2016, 1(1), 65-75; doi:10.3390/sinusitis1010065

LTD4 and TGF-β1 Induce the Expression of Metalloproteinase-1 in Chronic Rhinosinusitis via a Cysteinyl Leukotriene Receptor 1-Related Mechanism

1
Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, 9000 Ghent, Belgium
2
Department of Otorhinolaryngology, Head and Neck Surgery, Federal University of São Paulo, 05405-000 São Paulo, Brazil
3
Laboratory of Protein chemistry, Proteomics & Epigenetic Signaling, Department Biomedical Sciences, University of Antwerp, 2610 Wilrijk, Belgium
*
Author to whom correspondence should be addressed.
Academic Editor: César Picado
Received: 7 March 2016 / Revised: 15 April 2016 / Accepted: 29 April 2016 / Published: 19 May 2016
(This article belongs to the Special Issue Chronic Rhinosinusitis: Clinical and Immunological Research)
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Abstract

Background: Cysteinyl leukotrienes (CysLTs) play a crucial role in the pathogenesis of airway remodeling. The use of CysLTs receptor antagonists has been included in the management of asthma and rhinitis. However, despite the action of these compounds on leukotriene production has been well documented, their role in airway remodeling remains unclear. Objective: We aimed to investigate the capability of the leukotriene receptor antagonist Montelukast to inhibit MMPs release after CysLTs stimulation in nasal tissue fibroblasts. Methods: Fibroblasts were isolated from sinunasal tissue collected from five patients suffering of chronic rhinosinusitis without nasal polyposis. Cells were cultured and stimulated first with LTC4 and LTD4 (10−10, 10−8, 10−6 M) using as pre-stimulus 10 ng/mL of: IL-4, IL-13, or TGF-beta1 and in presence or absence of Montelukast (10−10, 10−8, 10−6 M). To evaluate the regulation of MMP-1 and TIMP-1 we used enzyme immunoassays and to evaluate CysLT1 receptor we used real time PCR. Results: LTD4 but not LTC4 induced production of mRNA for CysLT1 receptor in a dose dependent manner and with an additive effect when the cells where primed with TGF-β1. TNF-α, IL-4, and IL-13 did not influence the expression of the receptor. Levels of MMP-1 but not of TIMP-1 were statistically enhanced in cells primed with TGF-β1 and stimulated with LTD4. Montelukast significantly decreased Cys-LT1 receptor and MMP-1 concentrations in a dose-dependent way in cells stimulated with LTD4 and TGF-β1 separately and when they were applied together. Conclusion: The leukotriene pathway may play an important role in extra-cellular matrix formation in an inflamed environment, such as chronic sinusitis and, consequently, leukotriene receptor antagonists such as Montelukast may be of great benefit in management of this disease. View Full-Text
Keywords: chronic rhinosinusitis; cysteinyl leukotriene receptor 1; fibroblasts; metalloproteinase 1; Montelukast chronic rhinosinusitis; cysteinyl leukotriene receptor 1; fibroblasts; metalloproteinase 1; Montelukast
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Pezato, R.; Claeys, C.; Holtappels, G.; Bachert, C.; Pérez-Novo, C.A. LTD4 and TGF-β1 Induce the Expression of Metalloproteinase-1 in Chronic Rhinosinusitis via a Cysteinyl Leukotriene Receptor 1-Related Mechanism. Sinusitis 2016, 1, 65-75.

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