Cargando…

Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact thr...

Descripción completa

Detalles Bibliográficos
Autores principales: Januskevicius, Andrius, Gosens, Reinoud, Sakalauskas, Raimundas, Vaitkiene, Simona, Janulaityte, Ieva, Halayko, Andrew J., Hoppenot, Deimante, Malakauskas, Kestutis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220051/
https://www.ncbi.nlm.nih.gov/pubmed/28119625
http://dx.doi.org/10.3389/fphys.2016.00680
_version_ 1782492554053287936
author Januskevicius, Andrius
Gosens, Reinoud
Sakalauskas, Raimundas
Vaitkiene, Simona
Janulaityte, Ieva
Halayko, Andrew J.
Hoppenot, Deimante
Malakauskas, Kestutis
author_facet Januskevicius, Andrius
Gosens, Reinoud
Sakalauskas, Raimundas
Vaitkiene, Simona
Janulaityte, Ieva
Halayko, Andrew J.
Hoppenot, Deimante
Malakauskas, Kestutis
author_sort Januskevicius, Andrius
collection PubMed
description Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact through integrin–ligand interactions. Eosinophils express several types of outer membrane integrin, which are responsible for cell–cell and cell–extracellular matrix interactions. In our previous study we demonstrated that asthmatic eosinophils show increased adhesion to ASM cells and it may be important factor contributing to ASM remodeling in asthma. According to these findings, in the present study we investigated the effects of suppression of eosinophil integrin on eosinophil-induced ASM remodeling in asthma. Materials and Methods: Individual combined cell cultures of immortalized human ASM cells and eosinophils from peripheral blood of 22 asthmatic patients and 17 healthy controls were prepared. Eosinophil adhesion was evaluated using eosinophil peroxidase activity assay. Genes expression levels in ASM cells and eosinophils were measured using quantitative real-time PCR. ASM cell proliferation was measured using alamarBlue® solution. Eosinophil integrins were blocked by incubating with Arg-Gly-Asp-Ser peptide. Results: Eosinophils from the asthma group showed increased outer membrane α(4)β(1) and αMβ(2) integrin expression, increased adhesion to ASM cells, and overexpression of TGF-β(1) compared with eosinophils from the healthy control group. Blockade of eosinophil RGD-binding integrins by Arg-Gly-Asp-Ser peptide significantly reduced adhesion of eosinophils to ASM cells in both groups. Integrin-blocking decreased the effects of eosinophils on TGF-β(1), WNT-5a, and extracellular matrix protein gene expression in ASM cells and ASM cell proliferation in both groups. These effects were more pronounced in the asthma group compared with the control group. Conclusion: Suppression of eosinophil-ASM interaction via RGD-binding integrins attenuates eosinophil-induced ASM remodeling in asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT02648074.
format Online
Article
Text
id pubmed-5220051
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-52200512017-01-24 Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma Januskevicius, Andrius Gosens, Reinoud Sakalauskas, Raimundas Vaitkiene, Simona Janulaityte, Ieva Halayko, Andrew J. Hoppenot, Deimante Malakauskas, Kestutis Front Physiol Physiology Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact through integrin–ligand interactions. Eosinophils express several types of outer membrane integrin, which are responsible for cell–cell and cell–extracellular matrix interactions. In our previous study we demonstrated that asthmatic eosinophils show increased adhesion to ASM cells and it may be important factor contributing to ASM remodeling in asthma. According to these findings, in the present study we investigated the effects of suppression of eosinophil integrin on eosinophil-induced ASM remodeling in asthma. Materials and Methods: Individual combined cell cultures of immortalized human ASM cells and eosinophils from peripheral blood of 22 asthmatic patients and 17 healthy controls were prepared. Eosinophil adhesion was evaluated using eosinophil peroxidase activity assay. Genes expression levels in ASM cells and eosinophils were measured using quantitative real-time PCR. ASM cell proliferation was measured using alamarBlue® solution. Eosinophil integrins were blocked by incubating with Arg-Gly-Asp-Ser peptide. Results: Eosinophils from the asthma group showed increased outer membrane α(4)β(1) and αMβ(2) integrin expression, increased adhesion to ASM cells, and overexpression of TGF-β(1) compared with eosinophils from the healthy control group. Blockade of eosinophil RGD-binding integrins by Arg-Gly-Asp-Ser peptide significantly reduced adhesion of eosinophils to ASM cells in both groups. Integrin-blocking decreased the effects of eosinophils on TGF-β(1), WNT-5a, and extracellular matrix protein gene expression in ASM cells and ASM cell proliferation in both groups. These effects were more pronounced in the asthma group compared with the control group. Conclusion: Suppression of eosinophil-ASM interaction via RGD-binding integrins attenuates eosinophil-induced ASM remodeling in asthma. Trial Registration: ClinicalTrials.gov Identifier: NCT02648074. Frontiers Media S.A. 2017-01-09 /pmc/articles/PMC5220051/ /pubmed/28119625 http://dx.doi.org/10.3389/fphys.2016.00680 Text en Copyright © 2017 Januskevicius, Gosens, Sakalauskas, Vaitkiene, Janulaityte, Halayko, Hoppenot and Malakauskas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Januskevicius, Andrius
Gosens, Reinoud
Sakalauskas, Raimundas
Vaitkiene, Simona
Janulaityte, Ieva
Halayko, Andrew J.
Hoppenot, Deimante
Malakauskas, Kestutis
Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma
title Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma
title_full Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma
title_fullStr Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma
title_full_unstemmed Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma
title_short Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma
title_sort suppression of eosinophil integrins prevents remodeling of airway smooth muscle in asthma
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220051/
https://www.ncbi.nlm.nih.gov/pubmed/28119625
http://dx.doi.org/10.3389/fphys.2016.00680
work_keys_str_mv AT januskeviciusandrius suppressionofeosinophilintegrinspreventsremodelingofairwaysmoothmuscleinasthma
AT gosensreinoud suppressionofeosinophilintegrinspreventsremodelingofairwaysmoothmuscleinasthma
AT sakalauskasraimundas suppressionofeosinophilintegrinspreventsremodelingofairwaysmoothmuscleinasthma
AT vaitkienesimona suppressionofeosinophilintegrinspreventsremodelingofairwaysmoothmuscleinasthma
AT janulaityteieva suppressionofeosinophilintegrinspreventsremodelingofairwaysmoothmuscleinasthma
AT halaykoandrewj suppressionofeosinophilintegrinspreventsremodelingofairwaysmoothmuscleinasthma
AT hoppenotdeimante suppressionofeosinophilintegrinspreventsremodelingofairwaysmoothmuscleinasthma
AT malakauskaskestutis suppressionofeosinophilintegrinspreventsremodelingofairwaysmoothmuscleinasthma