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Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro

Kirsty Meldrum, Stephen Evans Orcid Logo, Michael Burgum, Shareen Doak Orcid Logo, Martin Clift Orcid Logo

Particle and Fibre Toxicology, Volume: 21, Issue: 1

Swansea University Authors: Kirsty Meldrum, Stephen Evans Orcid Logo, Michael Burgum, Shareen Doak Orcid Logo, Martin Clift Orcid Logo

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DOI (Published version): 10.1186/s12989-024-00584-8

Abstract

Exposure to indoor air pollutants (IAP) has increased recently, with people spending more time indoors (i.e. homes, offices, schools and transportation). Increased exposures of IAP on a healthy population are poorly understood, and those with allergic respiratory conditions even less so. The objecti...

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Published in: Particle and Fibre Toxicology
ISSN: 1743-8977
Published: Springer Science and Business Media LLC 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa66993
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Increased exposures of IAP on a healthy population are poorly understood, and those with allergic respiratory conditions even less so. The objective of this study, therefore, was to implement a well-characterised in vitro model of the human alveolar epithelial barrier (A549 + PMA differentiated THP-1 incubated with and without IL-13, IL-5 and IL-4) to determine the effects of a standardised indoor particulate (NIST 2583) on both a healthy lung model and one modelling a type-II (stimulated with IL-13, IL-5 and IL-4) inflammatory response(such as asthma). Using concentrations from the literature, and an environmentally appropriate exposure we investigated 232, 464 and 608ng/cm2 of NIST 2583 respectively. Membrane integrity (blue dextran), viability (trypan blue), genotoxicity (micronucleus (Mn) assay) and (pro-)/(anti-)inflammatory effects (IL-6, IL-8, IL-33, IL-10) were then assessed 24 h post exposure to both models. Models were exposed using a physiologically relevant aerosolisation method (VitroCell Cloud 12 exposure system). No changes in Mn frequency or membrane integrity in either model were noted when exposed to any of the tested concentrations of NIST 2583. A significant decrease (p &lt; 0.05) in cell viability at the highest concentration was observed in the healthy model. Whilst cell viability in the “inflamed” model was decreased at the lower concentrations (significantly (p &lt; 0.05) after 464ng/cm2). A significant reduction (p &lt; 0.05) in IL-10 and a significant increase in IL-33 was seen after 24 h exposure to NIST 2583 (464, 608ng/cm2) in the “inflamed” model. Collectively, the results indicate the potential for IAP to cause the onset of a type II response as well as exacerbating pre-existing allergic conditions. Furthermore, the data imposes the importance of considering unhealthy individuals when investigating the potential health effects of IAP. It also highlights that even in a healthy population these particles have the potential to induce this type II response and initiate an immune response following exposure to IAP.</abstract><type>Journal Article</type><journal>Particle and Fibre Toxicology</journal><volume>21</volume><journalNumber>1</journalNumber><paginationStart/><paginationEnd/><publisher>Springer Science and Business Media LLC</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>1743-8977</issnElectronic><keywords>Indoor air pollution, In vitro, Particulate matter, Inhalation, Lung, Disease model, Healthy</keywords><publishedDay>17</publishedDay><publishedMonth>5</publishedMonth><publishedYear>2024</publishedYear><publishedDate>2024-05-17</publishedDate><doi>10.1186/s12989-024-00584-8</doi><url>http://dx.doi.org/10.1186/s12989-024-00584-8</url><notes/><college>COLLEGE NANME</college><department>Medical School</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>MEDS</DepartmentCode><institution>Swansea University</institution><apcterm>SU Library paid the OA fee (TA Institutional Deal)</apcterm><funders>This study was funded and supported by the United Kingdom Environmental Mutagen Society (UKEMS) (UKEMS Small Grants Scheme for Feasibility awarded to KM), the UKRI (NERC) funded ’RESPIRE’ study (Grant No. NE/W002264/1)</funders><projectreference>Grant No. NE/W002264/1</projectreference><lastEdited>2024-07-09T09:02:05.8407313</lastEdited><Created>2024-07-09T08:53:44.0700912</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Biomedical Science</level></path><authors><author><firstname>Kirsty</firstname><surname>Meldrum</surname><order>1</order></author><author><firstname>Stephen</firstname><surname>Evans</surname><orcid>0000-0002-5352-9800</orcid><order>2</order></author><author><firstname>Michael</firstname><surname>Burgum</surname><order>3</order></author><author><firstname>Shareen</firstname><surname>Doak</surname><orcid>0000-0002-6753-1987</orcid><order>4</order></author><author><firstname>Martin</firstname><surname>Clift</surname><orcid>0000-0001-6133-3368</orcid><order>5</order></author></authors><documents/><OutputDurs><OutputDur><Id>260</Id><IsDataAvailableOnline xsi:nil="true"/><DataNotAvailableOnlineReasonId xsi:nil="true"/><IsDurRestrictions xsi:nil="true"/><DurRestrictionReasonId xsi:nil="true"/><DurEmbargoDate xsi:nil="true"/></OutputDur></OutputDurs></rfc1807>
spelling v2 66993 2024-07-09 Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro bbb7bd27bfa3c6ffc73da8facfebc793 Kirsty Meldrum Kirsty Meldrum true false cfca981bdfb8492873a48cc1629def9a 0000-0002-5352-9800 Stephen Evans Stephen Evans true false d3fe156a5ee169e586b8bad6ae4cb1d8 Michael Burgum Michael Burgum true false 8f70286908f67238a527a98cbf66d387 0000-0002-6753-1987 Shareen Doak Shareen Doak true false 71bf49b157691e541950f5c3f49c9169 0000-0001-6133-3368 Martin Clift Martin Clift true false 2024-07-09 MEDS Exposure to indoor air pollutants (IAP) has increased recently, with people spending more time indoors (i.e. homes, offices, schools and transportation). Increased exposures of IAP on a healthy population are poorly understood, and those with allergic respiratory conditions even less so. The objective of this study, therefore, was to implement a well-characterised in vitro model of the human alveolar epithelial barrier (A549 + PMA differentiated THP-1 incubated with and without IL-13, IL-5 and IL-4) to determine the effects of a standardised indoor particulate (NIST 2583) on both a healthy lung model and one modelling a type-II (stimulated with IL-13, IL-5 and IL-4) inflammatory response(such as asthma). Using concentrations from the literature, and an environmentally appropriate exposure we investigated 232, 464 and 608ng/cm2 of NIST 2583 respectively. Membrane integrity (blue dextran), viability (trypan blue), genotoxicity (micronucleus (Mn) assay) and (pro-)/(anti-)inflammatory effects (IL-6, IL-8, IL-33, IL-10) were then assessed 24 h post exposure to both models. Models were exposed using a physiologically relevant aerosolisation method (VitroCell Cloud 12 exposure system). No changes in Mn frequency or membrane integrity in either model were noted when exposed to any of the tested concentrations of NIST 2583. A significant decrease (p < 0.05) in cell viability at the highest concentration was observed in the healthy model. Whilst cell viability in the “inflamed” model was decreased at the lower concentrations (significantly (p < 0.05) after 464ng/cm2). A significant reduction (p < 0.05) in IL-10 and a significant increase in IL-33 was seen after 24 h exposure to NIST 2583 (464, 608ng/cm2) in the “inflamed” model. Collectively, the results indicate the potential for IAP to cause the onset of a type II response as well as exacerbating pre-existing allergic conditions. Furthermore, the data imposes the importance of considering unhealthy individuals when investigating the potential health effects of IAP. It also highlights that even in a healthy population these particles have the potential to induce this type II response and initiate an immune response following exposure to IAP. Journal Article Particle and Fibre Toxicology 21 1 Springer Science and Business Media LLC 1743-8977 Indoor air pollution, In vitro, Particulate matter, Inhalation, Lung, Disease model, Healthy 17 5 2024 2024-05-17 10.1186/s12989-024-00584-8 http://dx.doi.org/10.1186/s12989-024-00584-8 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) This study was funded and supported by the United Kingdom Environmental Mutagen Society (UKEMS) (UKEMS Small Grants Scheme for Feasibility awarded to KM), the UKRI (NERC) funded ’RESPIRE’ study (Grant No. NE/W002264/1) Grant No. NE/W002264/1 2024-07-09T09:02:05.8407313 2024-07-09T08:53:44.0700912 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Kirsty Meldrum 1 Stephen Evans 0000-0002-5352-9800 2 Michael Burgum 3 Shareen Doak 0000-0002-6753-1987 4 Martin Clift 0000-0001-6133-3368 5 260
title Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro
spellingShingle Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro
Kirsty Meldrum
Stephen Evans
Michael Burgum
Shareen Doak
Martin Clift
title_short Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro
title_full Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro
title_fullStr Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro
title_full_unstemmed Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro
title_sort Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro
author_id_str_mv bbb7bd27bfa3c6ffc73da8facfebc793
cfca981bdfb8492873a48cc1629def9a
d3fe156a5ee169e586b8bad6ae4cb1d8
8f70286908f67238a527a98cbf66d387
71bf49b157691e541950f5c3f49c9169
author_id_fullname_str_mv bbb7bd27bfa3c6ffc73da8facfebc793_***_Kirsty Meldrum
cfca981bdfb8492873a48cc1629def9a_***_Stephen Evans
d3fe156a5ee169e586b8bad6ae4cb1d8_***_Michael Burgum
8f70286908f67238a527a98cbf66d387_***_Shareen Doak
71bf49b157691e541950f5c3f49c9169_***_Martin Clift
author Kirsty Meldrum
Stephen Evans
Michael Burgum
Shareen Doak
Martin Clift
author2 Kirsty Meldrum
Stephen Evans
Michael Burgum
Shareen Doak
Martin Clift
format Journal article
container_title Particle and Fibre Toxicology
container_volume 21
container_issue 1
publishDate 2024
institution Swansea University
issn 1743-8977
doi_str_mv 10.1186/s12989-024-00584-8
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
url http://dx.doi.org/10.1186/s12989-024-00584-8
document_store_str 0
active_str 0
description Exposure to indoor air pollutants (IAP) has increased recently, with people spending more time indoors (i.e. homes, offices, schools and transportation). Increased exposures of IAP on a healthy population are poorly understood, and those with allergic respiratory conditions even less so. The objective of this study, therefore, was to implement a well-characterised in vitro model of the human alveolar epithelial barrier (A549 + PMA differentiated THP-1 incubated with and without IL-13, IL-5 and IL-4) to determine the effects of a standardised indoor particulate (NIST 2583) on both a healthy lung model and one modelling a type-II (stimulated with IL-13, IL-5 and IL-4) inflammatory response(such as asthma). Using concentrations from the literature, and an environmentally appropriate exposure we investigated 232, 464 and 608ng/cm2 of NIST 2583 respectively. Membrane integrity (blue dextran), viability (trypan blue), genotoxicity (micronucleus (Mn) assay) and (pro-)/(anti-)inflammatory effects (IL-6, IL-8, IL-33, IL-10) were then assessed 24 h post exposure to both models. Models were exposed using a physiologically relevant aerosolisation method (VitroCell Cloud 12 exposure system). No changes in Mn frequency or membrane integrity in either model were noted when exposed to any of the tested concentrations of NIST 2583. A significant decrease (p < 0.05) in cell viability at the highest concentration was observed in the healthy model. Whilst cell viability in the “inflamed” model was decreased at the lower concentrations (significantly (p < 0.05) after 464ng/cm2). A significant reduction (p < 0.05) in IL-10 and a significant increase in IL-33 was seen after 24 h exposure to NIST 2583 (464, 608ng/cm2) in the “inflamed” model. Collectively, the results indicate the potential for IAP to cause the onset of a type II response as well as exacerbating pre-existing allergic conditions. Furthermore, the data imposes the importance of considering unhealthy individuals when investigating the potential health effects of IAP. It also highlights that even in a healthy population these particles have the potential to induce this type II response and initiate an immune response following exposure to IAP.
published_date 2024-05-17T09:02:05Z
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