Back to Journals » International Journal of Chronic Obstructive Pulmonary Disease » Volume 5

Tiotropium bromide inhibits TGF-ß-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro

Authors Kazuhito Asano, Yusuke Shikama, Naruo Shoji, et al.

Published 30 August 2010 Volume 2010:5 Pages 277—286

DOI https://doi.org/10.2147/COPD.S11737

Review by Single-blind

Peer reviewer comments 7

Kazuhito Asano1, Yusuke Shikama2, Naruo Shoji3, Kojiro Hirano3, Harumi Suzaki3, Hiroaki Nakajima2

1Division of Physiology, School of Nursing and Rehabilitation Sciences, Showa University, Yokohama, Japan; 2Department of Respiratory Diseases, Showa University Northern Yokohamashi Hospital, Yokohama, Japan; 3Department of Otorhinolaryngology, School of Medicine, Showa University, Tokyo, Japan

Background: Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and structural alterations (ie, tissue remodeling) throughout the conducting airways, parenchyma, and pulmonary vasculature. Matrix metalloproteinases (MMPs) are extracellular degrading enzymes that play a critical role in inflammatory cell infiltration and tissue ­remodeling, but the influence of the agents that are used for the treatment of COPD on the production of MMPs is not well understood.

Purpose:
The present study aimed to examine the influence of tiotropium bromide hydrate (TBH) on the production of MMPs from lung fibroblasts (LFs) induced by transforming growth factor (TGF)-ß in vitro.

Methods:
LFs, at a concentration of 5 × 105 cells·mL-1, were stimulated with TGF-ß in the presence of various concentrations of TBH. MMP-1 and MMP-2 levels in culture ­supernatants were examined by enzyme-linked immunosorbent assay (ELISA), and MMP messenger ribonucleic acid (mRNA) expression was examined by real-time polymerase chain reaction (RT-PCR). The influence of TBH on TGF-ß signaling pathways was also analyzed by ­examining Smad activation and signaling protein phosphorylation by ELISA.

Results:
TBH at more than 15 pg·mL-1 inhibited the production of MMP-1 and MMP-2, but not tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2, from LFs, after TGF-ß stimulation. TBH also suppressed MMP mRNA expression through the inhibition of Smad activation and signaling protein, extracellular-signal-regulated kinase (ERK) 1 and 2, and c-Jun N-terminal kinase (JNK), phosphorylation.

Conclusion:
These results may suggest that TBH suppresses MMP production from LFs, through interference of TGF-ß-mediated signaling pathways and results in favorable modification of the clinical status of COPD.

Keywords:
tiotropium bromide, matrix metalloproteinases, lung fibroblast, TGF-ß, inhibition, in vitro

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF] 

 

Other articles by this author:

Suppression of IL-8 production from airway cells by tiotropium bromide in vitro

Suzaki I, Asano K, Shikama Y, Hamasaki T, Kanei A, Suzaki H

International Journal of Chronic Obstructive Pulmonary Disease 2011, 6:439-448

Published Date: 6 September 2011

Suppressive activity of tiotropium bromide on matrix metalloproteinase production from lung fibroblasts in vitro

Kazuhito Asano, Yusuke Shikama, Yasuhiro Shibuya, Hiroaki Nakajima, Ken-ichi Kanai, et al

International Journal of Chronic Obstructive Pulmonary Disease 2008, 3:781-790

Published Date: 5 December 2008

Readers of this article also read:

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010