Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of Asthma Article Swipe
Je‐Oh Lim
,
Sejin Lee
,
Woong‐Il Kim
,
So‐Won Pak
,
Changjong Moon
,
In‐Sik Shin
,
Jeong‐Doo Heo
,
Je‐Won Ko
,
Jong-Choon Kim
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/ijms22189924
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.3390/ijms22189924
Titanium dioxide nanoparticles (TiO2NPs) are widely used in industrial and medicinal fields and in various consumer products, and their increasing use has led to an increase in the number of toxicity studies; however, studies investigating the underlying toxicity mechanism have been rare. In this study, we evaluated potential toxic effects of TiO2NPs exposure on lungs as well as the development of asthma through the ovalbumin (OVA)-induced mouse model of asthma. Furthermore, we also investigated the associated toxic mechanism. TiO2NPs caused pulmonary toxicity by exacerbating the inflammatory response, indicated by an increase in the number and level of inflammatory cells and mediators, respectively. OVA-induced asthma exposed mice to TiO2NPs led to significant increases in inflammatory mediators, cytokines, and airway hyperresponsiveness compared with those in non-exposed asthmatic mice. This was also accompanied by increased inflammatory cell infiltration and mucus production in the lung tissues. Additionally, TiO2NPs decreased the expression of B-cell lymphoma 2 (Bcl2) and the expressions of thioredoxin-interacting protein (TXNIP), phospho-apoptosis signal-regulating kinase 1, Bcl2-associated X, and cleaved-caspase 3 were escalated in the lungs of asthmatic mice compared with those in non-exposed asthmatic mice. These responses were consistent with in vitro results obtained using human airway epithelial cells. TiO2NPs treated cells exhibited an increase in the mRNA and protein expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α with an elevation of TXNIP signaling compared to non-treated cells. Moreover, pathophysiological changes induced by TiO2NP treatment were significantly decreased by TXNIP knockdown in airway epithelial cells. Overall, TiO2NP exposure induced toxicological changes in the respiratory tract and exacerbated the development of asthma via activation of the TXNIP-apoptosis pathway. These results provide insights into the underlying mechanism of TiO2NP-mediated respiratory toxicity.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/ijms22189924
- https://www.mdpi.com/1422-0067/22/18/9924/pdf?version=1631623024
- OA Status
- gold
- Cited By
- 21
- References
- 33
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3188085932
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W3188085932Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/ijms22189924Digital Object Identifier
- Title
-
Titanium Dioxide Nanoparticles Exacerbate Allergic Airway Inflammation via TXNIP Upregulation in a Mouse Model of AsthmaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2021Year of publication
- Publication date
-
2021-09-14Full publication date if available
- Authors
-
Je‐Oh Lim, Sejin Lee, Woong‐Il Kim, So‐Won Pak, Changjong Moon, In‐Sik Shin, Jeong‐Doo Heo, Je‐Won Ko, Jong-Choon KimList of authors in order
- Landing page
-
https://doi.org/10.3390/ijms22189924Publisher landing page
- PDF URL
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https://www.mdpi.com/1422-0067/22/18/9924/pdf?version=1631623024Direct link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/1422-0067/22/18/9924/pdf?version=1631623024Direct OA link when available
- Concepts
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Ovalbumin, Medicine, TXNIP, Proinflammatory cytokine, Inflammation, Tumor necrosis factor alpha, Immunology, Cancer research, Oxidative stress, Immune system, Internal medicine, ThioredoxinTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
21Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 6, 2023: 5, 2022: 5Per-year citation counts (last 5 years)
- References (count)
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33Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.led | 22, 108 |
| abstract_inverted_index.the | 27, 35, 58, 63, 74, 84, 92, 139, 145, 153, 171, 204, 251, 256, 263, 271 |
| abstract_inverted_index.use | 20 |
| abstract_inverted_index.via | 260 |
| abstract_inverted_index.was | 127 |
| abstract_inverted_index.This | 126 |
| abstract_inverted_index.also | 72, 128 |
| abstract_inverted_index.been | 40 |
| abstract_inverted_index.cell | 133 |
| abstract_inverted_index.have | 39 |
| abstract_inverted_index.into | 270 |
| abstract_inverted_index.lung | 140 |
| abstract_inverted_index.mRNA | 205 |
| abstract_inverted_index.mice | 105, 175 |
| abstract_inverted_index.this | 43 |
| abstract_inverted_index.used | 6 |
| abstract_inverted_index.well | 56 |
| abstract_inverted_index.were | 168, 185, 234 |
| abstract_inverted_index.with | 120, 177, 187, 217 |
| abstract_inverted_index.IL-6, | 212 |
| abstract_inverted_index.TXNIP | 221, 238 |
| abstract_inverted_index.These | 183, 266 |
| abstract_inverted_index.cells | 98, 199 |
| abstract_inverted_index.human | 193 |
| abstract_inverted_index.level | 95 |
| abstract_inverted_index.lungs | 54, 172 |
| abstract_inverted_index.mice. | 125, 182 |
| abstract_inverted_index.model | 67 |
| abstract_inverted_index.mouse | 66 |
| abstract_inverted_index.mucus | 136 |
| abstract_inverted_index.rare. | 41 |
| abstract_inverted_index.their | 18 |
| abstract_inverted_index.those | 121, 178 |
| abstract_inverted_index.toxic | 48, 76 |
| abstract_inverted_index.tract | 253 |
| abstract_inverted_index.tumor | 214 |
| abstract_inverted_index.using | 192 |
| abstract_inverted_index.vitro | 189 |
| abstract_inverted_index.(Bcl2) | 151 |
| abstract_inverted_index.B-cell | 148 |
| abstract_inverted_index.TiO2NP | 232, 245 |
| abstract_inverted_index.airway | 117, 194, 241 |
| abstract_inverted_index.asthma | 61, 103, 259 |
| abstract_inverted_index.caused | 79 |
| abstract_inverted_index.cells. | 196, 226, 243 |
| abstract_inverted_index.fields | 11 |
| abstract_inverted_index.kinase | 161 |
| abstract_inverted_index.number | 28, 93 |
| abstract_inverted_index.study, | 44 |
| abstract_inverted_index.widely | 5 |
| abstract_inverted_index.TiO2NPs | 51, 78, 107, 143, 197 |
| abstract_inverted_index.asthma. | 69 |
| abstract_inverted_index.changes | 229, 249 |
| abstract_inverted_index.dioxide | 1 |
| abstract_inverted_index.effects | 49 |
| abstract_inverted_index.exposed | 104 |
| abstract_inverted_index.induced | 230, 247 |
| abstract_inverted_index.protein | 157, 207 |
| abstract_inverted_index.provide | 268 |
| abstract_inverted_index.results | 190, 267 |
| abstract_inverted_index.studies | 33 |
| abstract_inverted_index.through | 62 |
| abstract_inverted_index.treated | 198 |
| abstract_inverted_index.various | 14 |
| abstract_inverted_index.(TXNIP), | 158 |
| abstract_inverted_index.Overall, | 244 |
| abstract_inverted_index.Titanium | 0 |
| abstract_inverted_index.compared | 119, 176, 223 |
| abstract_inverted_index.consumer | 15 |
| abstract_inverted_index.exposure | 52, 246 |
| abstract_inverted_index.however, | 32 |
| abstract_inverted_index.increase | 25, 90, 202 |
| abstract_inverted_index.insights | 269 |
| abstract_inverted_index.lymphoma | 149 |
| abstract_inverted_index.necrosis | 215 |
| abstract_inverted_index.obtained | 191 |
| abstract_inverted_index.pathway. | 265 |
| abstract_inverted_index.studies; | 31 |
| abstract_inverted_index.tissues. | 141 |
| abstract_inverted_index.toxicity | 30, 37, 81 |
| abstract_inverted_index.(IL)-1β, | 211 |
| abstract_inverted_index.(TiO2NPs) | 3 |
| abstract_inverted_index.Moreover, | 227 |
| abstract_inverted_index.asthmatic | 124, 174, 181 |
| abstract_inverted_index.decreased | 144, 236 |
| abstract_inverted_index.elevation | 219 |
| abstract_inverted_index.escalated | 169 |
| abstract_inverted_index.evaluated | 46 |
| abstract_inverted_index.exhibited | 200 |
| abstract_inverted_index.factor-α | 216 |
| abstract_inverted_index.increased | 131 |
| abstract_inverted_index.increases | 111 |
| abstract_inverted_index.indicated | 87 |
| abstract_inverted_index.knockdown | 239 |
| abstract_inverted_index.mechanism | 38, 273 |
| abstract_inverted_index.medicinal | 10 |
| abstract_inverted_index.ovalbumin | 64 |
| abstract_inverted_index.potential | 47 |
| abstract_inverted_index.products, | 16 |
| abstract_inverted_index.pulmonary | 80 |
| abstract_inverted_index.response, | 86 |
| abstract_inverted_index.responses | 184 |
| abstract_inverted_index.signaling | 222 |
| abstract_inverted_index.toxicity. | 277 |
| abstract_inverted_index.treatment | 233 |
| abstract_inverted_index.activation | 261 |
| abstract_inverted_index.associated | 75 |
| abstract_inverted_index.consistent | 186 |
| abstract_inverted_index.cytokines, | 115 |
| abstract_inverted_index.epithelial | 195, 242 |
| abstract_inverted_index.expression | 146, 208 |
| abstract_inverted_index.increasing | 19 |
| abstract_inverted_index.industrial | 8 |
| abstract_inverted_index.mechanism. | 77 |
| abstract_inverted_index.mediators, | 100, 114 |
| abstract_inverted_index.production | 137 |
| abstract_inverted_index.underlying | 36, 272 |
| abstract_inverted_index.OVA-induced | 102 |
| abstract_inverted_index.accompanied | 129 |
| abstract_inverted_index.development | 59, 257 |
| abstract_inverted_index.exacerbated | 255 |
| abstract_inverted_index.expressions | 154 |
| abstract_inverted_index.interleukin | 210 |
| abstract_inverted_index.non-exposed | 123, 180 |
| abstract_inverted_index.non-treated | 225 |
| abstract_inverted_index.respiratory | 252, 276 |
| abstract_inverted_index.significant | 110 |
| abstract_inverted_index.Furthermore, | 70 |
| abstract_inverted_index.exacerbating | 83 |
| abstract_inverted_index.infiltration | 134 |
| abstract_inverted_index.inflammatory | 85, 97, 113, 132 |
| abstract_inverted_index.investigated | 73 |
| abstract_inverted_index.(OVA)-induced | 65 |
| abstract_inverted_index.Additionally, | 142 |
| abstract_inverted_index.investigating | 34 |
| abstract_inverted_index.nanoparticles | 2 |
| abstract_inverted_index.respectively. | 101 |
| abstract_inverted_index.significantly | 235 |
| abstract_inverted_index.toxicological | 248 |
| abstract_inverted_index.Bcl2-associated | 163 |
| abstract_inverted_index.TXNIP-apoptosis | 264 |
| abstract_inverted_index.TiO2NP-mediated | 275 |
| abstract_inverted_index.cleaved-caspase | 166 |
| abstract_inverted_index.phospho-apoptosis | 159 |
| abstract_inverted_index.signal-regulating | 160 |
| abstract_inverted_index.pathophysiological | 228 |
| abstract_inverted_index.hyperresponsiveness | 118 |
| abstract_inverted_index.thioredoxin-interacting | 156 |
| cited_by_percentile_year.max | 98 |
| cited_by_percentile_year.min | 97 |
| corresponding_author_ids | https://openalex.org/A5049627091, https://openalex.org/A5089989506 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 9 |
| corresponding_institution_ids | https://openalex.org/I111277659, https://openalex.org/I196345858 |
| citation_normalized_percentile.value | 0.81884171 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |