Particulate matter from car exhaust alters function of human iPSC-derived microglia
Abstract Background Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Al...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12989-024-00564-y |
| _version_ | 1827328806625476608 |
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| author | Henna Jäntti Steffi Jonk Mireia Gómez Budia Sohvi Ohtonen Ilkka Fagerlund Mohammad Feroze Fazaludeen Päivi Aakko-Saksa Alice Pebay Šárka Lehtonen Jari Koistinaho Katja M. Kanninen Pasi I. Jalava Tarja Malm Paula Korhonen |
| author_facet | Henna Jäntti Steffi Jonk Mireia Gómez Budia Sohvi Ohtonen Ilkka Fagerlund Mohammad Feroze Fazaludeen Päivi Aakko-Saksa Alice Pebay Šárka Lehtonen Jari Koistinaho Katja M. Kanninen Pasi I. Jalava Tarja Malm Paula Korhonen |
| author_sort | Henna Jäntti |
| collection | DOAJ |
| description | Abstract Background Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer’s disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia. Results Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml−1 increased microglial survival whereas higher concentrations became toxic over time. Both tested pollutants impaired microglial phagocytosis and increased secretion of a few proinflammatory cytokines with distinct patterns, compared to lipopolysaccharide induced responses. iMGLs showed pollutant dependent responses to production of reactive oxygen species (ROS) with CNG inducing and EN590 reducing ROS production. Conclusions Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents. |
| first_indexed | 2024-03-07T15:23:37Z |
| format | Article |
| id | doaj.art-2ffcedbcf3f049898ce5fdfb9dd94b96 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-03-07T15:23:37Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-2ffcedbcf3f049898ce5fdfb9dd94b962024-03-05T17:25:48ZengBMCParticle and Fibre Toxicology1743-89772024-02-0121112110.1186/s12989-024-00564-yParticulate matter from car exhaust alters function of human iPSC-derived microgliaHenna Jäntti0Steffi Jonk1Mireia Gómez Budia2Sohvi Ohtonen3Ilkka Fagerlund4Mohammad Feroze Fazaludeen5Päivi Aakko-Saksa6Alice Pebay7Šárka Lehtonen8Jari Koistinaho9Katja M. Kanninen10Pasi I. Jalava11Tarja Malm12Paula Korhonen13A.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandDivision of Eye and Vision, Department of Clinical Neuroscience, St. Erik Eye Hospital, Karolinska InstitutetA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandVTT Technical Research Centre of FinlandDepartment of Surgery, Royal Melbourne Hospital, The University of MelbourneA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandNeuroscience Center, University of HelsinkiA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandDepartment of Environmental and Biological Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern FinlandAbstract Background Air pollution is recognized as an emerging environmental risk factor for neurological diseases. Large-scale epidemiological studies associate traffic-related particulate matter (PM) with impaired cognitive functions and increased incidence of neurodegenerative diseases such as Alzheimer’s disease. Inhaled components of PM may directly invade the brain via the olfactory route, or act through peripheral system responses resulting in inflammation and oxidative stress in the brain. Microglia are the immune cells of the brain implicated in the progression of neurodegenerative diseases. However, it remains unknown how PM affects live human microglia. Results Here we show that two different PMs derived from exhausts of cars running on EN590 diesel or compressed natural gas (CNG) alter the function of human microglia-like cells in vitro. We exposed human induced pluripotent stem cell (iPSC)-derived microglia-like cells (iMGLs) to traffic related PMs and explored their functional responses. Lower concentrations of PMs ranging between 10 and 100 µg ml−1 increased microglial survival whereas higher concentrations became toxic over time. Both tested pollutants impaired microglial phagocytosis and increased secretion of a few proinflammatory cytokines with distinct patterns, compared to lipopolysaccharide induced responses. iMGLs showed pollutant dependent responses to production of reactive oxygen species (ROS) with CNG inducing and EN590 reducing ROS production. Conclusions Our study indicates that traffic-related air pollutants alter the function of human microglia and warrant further studies to determine whether these changes contribute to adverse effects in the brain and on cognition over time. This study demonstrates human iPSC-microglia as a valuable tool to study functional microglial responses to environmental agents.https://doi.org/10.1186/s12989-024-00564-yMicrogliaParticulate matterTraffic-relatediPSCiPSC-microgliaNeuroinflammation |
| spellingShingle | Henna Jäntti Steffi Jonk Mireia Gómez Budia Sohvi Ohtonen Ilkka Fagerlund Mohammad Feroze Fazaludeen Päivi Aakko-Saksa Alice Pebay Šárka Lehtonen Jari Koistinaho Katja M. Kanninen Pasi I. Jalava Tarja Malm Paula Korhonen Particulate matter from car exhaust alters function of human iPSC-derived microglia Particle and Fibre Toxicology Microglia Particulate matter Traffic-related iPSC iPSC-microglia Neuroinflammation |
| title | Particulate matter from car exhaust alters function of human iPSC-derived microglia |
| title_full | Particulate matter from car exhaust alters function of human iPSC-derived microglia |
| title_fullStr | Particulate matter from car exhaust alters function of human iPSC-derived microglia |
| title_full_unstemmed | Particulate matter from car exhaust alters function of human iPSC-derived microglia |
| title_short | Particulate matter from car exhaust alters function of human iPSC-derived microglia |
| title_sort | particulate matter from car exhaust alters function of human ipsc derived microglia |
| topic | Microglia Particulate matter Traffic-related iPSC iPSC-microglia Neuroinflammation |
| url | https://doi.org/10.1186/s12989-024-00564-y |
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