Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2
Abstract TSLP-regulated Park2 and mitophagy may be critical underlying driver of asthma exacerbations, as well as eosinophil responses to oral corticosteroids (OCS). However, detailed molecular knowledge of the molecular mechanisms involved is lacking. In a prospective cohort study at ED Siriraj Hos...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-07102-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849768971340873728 |
|---|---|
| author | Kittipong Maneechotesuwan Jirawat Assawabhumi Jirabhorn Chankham Kanda Kasetsinsombat Khin Su Su Htwe Ian M. Adcock |
| author_facet | Kittipong Maneechotesuwan Jirawat Assawabhumi Jirabhorn Chankham Kanda Kasetsinsombat Khin Su Su Htwe Ian M. Adcock |
| author_sort | Kittipong Maneechotesuwan |
| collection | DOAJ |
| description | Abstract TSLP-regulated Park2 and mitophagy may be critical underlying driver of asthma exacerbations, as well as eosinophil responses to oral corticosteroids (OCS). However, detailed molecular knowledge of the molecular mechanisms involved is lacking. In a prospective cohort study at ED Siriraj Hospital, 28 consecutive patients with an acute asthma exacerbation were administered OCS treatment for one week. Serum levels of TSLP, Park2, Mul1, related cytokines, mitochondrial DNA (mtDNA), and oxidative stress were measured. The effects of TSLP, inhaled corticosteroids, NLRP3 inflammasome inhibitor, and mitochondrial-targeted antioxidant on mitophagy, mtDNA release, Park2, and Mul1 were examined in blood monocytes and in a human bronchial epithelial cell line (HBEC). Two distinct eosinophil responses to OCS treatment were observed: reduced (RE) and increased absolute blood eosinophil levels (IE). Following OCS treatment, participants with IE demonstrated stable TSLP levels and a significant rise in Park2. The IE group exhibited markedly higher baseline oxidative stress levels than the RE group at an exacerbation episode and further increase in oxidative stress after OCS treatment. TSLP augmented the induction of Park2 while inhibiting mitophagy, resulting in increased release of mtDNA from blood monocytes and human bronchial epithelial cells and stimulating inflammasome activation. Corticosteroids did not effectively suppress oxidative stress-mediated TSLP effects. The present study demonstrated potential inflammatory mechanisms in acute asthmatics with rising eosinophil counts following OCS treatment including a possible role of TSLP in suppressing mitophagy and inducing mtDNA release with concomitant inflammasome activation, and Park2 expression. |
| format | Article |
| id | doaj-art-944eea262980416d907e4fbf5e9b34ef |
| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-944eea262980416d907e4fbf5e9b34ef2025-08-20T03:03:37ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-07102-6Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2Kittipong Maneechotesuwan0Jirawat Assawabhumi1Jirabhorn Chankham2Kanda Kasetsinsombat3Khin Su Su Htwe4Ian M. Adcock5Division of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDivision of Respiratory Disease and Tuberculosis, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Emergency Medicine, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityDepartment of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol UniversityAirway Disease Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College LondonAbstract TSLP-regulated Park2 and mitophagy may be critical underlying driver of asthma exacerbations, as well as eosinophil responses to oral corticosteroids (OCS). However, detailed molecular knowledge of the molecular mechanisms involved is lacking. In a prospective cohort study at ED Siriraj Hospital, 28 consecutive patients with an acute asthma exacerbation were administered OCS treatment for one week. Serum levels of TSLP, Park2, Mul1, related cytokines, mitochondrial DNA (mtDNA), and oxidative stress were measured. The effects of TSLP, inhaled corticosteroids, NLRP3 inflammasome inhibitor, and mitochondrial-targeted antioxidant on mitophagy, mtDNA release, Park2, and Mul1 were examined in blood monocytes and in a human bronchial epithelial cell line (HBEC). Two distinct eosinophil responses to OCS treatment were observed: reduced (RE) and increased absolute blood eosinophil levels (IE). Following OCS treatment, participants with IE demonstrated stable TSLP levels and a significant rise in Park2. The IE group exhibited markedly higher baseline oxidative stress levels than the RE group at an exacerbation episode and further increase in oxidative stress after OCS treatment. TSLP augmented the induction of Park2 while inhibiting mitophagy, resulting in increased release of mtDNA from blood monocytes and human bronchial epithelial cells and stimulating inflammasome activation. Corticosteroids did not effectively suppress oxidative stress-mediated TSLP effects. The present study demonstrated potential inflammatory mechanisms in acute asthmatics with rising eosinophil counts following OCS treatment including a possible role of TSLP in suppressing mitophagy and inducing mtDNA release with concomitant inflammasome activation, and Park2 expression.https://doi.org/10.1038/s41598-025-07102-6Asthma exacerbationMitophagyMitochondrial DNAPark2Thymic stromal lymphopoietin |
| spellingShingle | Kittipong Maneechotesuwan Jirawat Assawabhumi Jirabhorn Chankham Kanda Kasetsinsombat Khin Su Su Htwe Ian M. Adcock Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2 Scientific Reports Asthma exacerbation Mitophagy Mitochondrial DNA Park2 Thymic stromal lymphopoietin |
| title | Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2 |
| title_full | Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2 |
| title_fullStr | Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2 |
| title_full_unstemmed | Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2 |
| title_short | Increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer ER stays and persisting thymic stromal lymphopoietin and increased Park2 |
| title_sort | increased eosinophils after oral corticosteroid treatment for asthma exacerbation correlated with longer er stays and persisting thymic stromal lymphopoietin and increased park2 |
| topic | Asthma exacerbation Mitophagy Mitochondrial DNA Park2 Thymic stromal lymphopoietin |
| url | https://doi.org/10.1038/s41598-025-07102-6 |
| work_keys_str_mv | AT kittipongmaneechotesuwan increasedeosinophilsafteroralcorticosteroidtreatmentforasthmaexacerbationcorrelatedwithlongererstaysandpersistingthymicstromallymphopoietinandincreasedpark2 AT jirawatassawabhumi increasedeosinophilsafteroralcorticosteroidtreatmentforasthmaexacerbationcorrelatedwithlongererstaysandpersistingthymicstromallymphopoietinandincreasedpark2 AT jirabhornchankham increasedeosinophilsafteroralcorticosteroidtreatmentforasthmaexacerbationcorrelatedwithlongererstaysandpersistingthymicstromallymphopoietinandincreasedpark2 AT kandakasetsinsombat increasedeosinophilsafteroralcorticosteroidtreatmentforasthmaexacerbationcorrelatedwithlongererstaysandpersistingthymicstromallymphopoietinandincreasedpark2 AT khinsusuhtwe increasedeosinophilsafteroralcorticosteroidtreatmentforasthmaexacerbationcorrelatedwithlongererstaysandpersistingthymicstromallymphopoietinandincreasedpark2 AT ianmadcock increasedeosinophilsafteroralcorticosteroidtreatmentforasthmaexacerbationcorrelatedwithlongererstaysandpersistingthymicstromallymphopoietinandincreasedpark2 |