IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation
<p>Abstract</p> <p>Background</p> <p>Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Therefore, we sought to determine whether TSLP could activate eosinophils, focusing on measuring the regulation of TSLPR expressio...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2012-07-01
|
Series: | Clinical and Molecular Allergy |
Subjects: | |
Online Access: | http://www.clinicalmolecularallergy.com/content/10/1/8 |
id |
doaj-3f2eb0d6ef894dd38fd56e702b75afee |
---|---|
record_format |
Article |
spelling |
doaj-3f2eb0d6ef894dd38fd56e702b75afee2020-11-25T01:04:44ZengBMCClinical and Molecular Allergy1476-79612012-07-01101810.1186/1476-7961-10-8IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulationCook Ellen BStahl James LSchwantes Elizabeth AFox Kristen EMathur Sameer K<p>Abstract</p> <p>Background</p> <p>Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Therefore, we sought to determine whether TSLP could activate eosinophils, focusing on measuring the regulation of TSLPR expression on eosinophils and degranulation in response to TSLP, as well as other eosinophil activation responses.</p> <p>Methods</p> <p>Eosinophil mRNA expression of TSLPR and IL-7Rα was examined by real-time quantitative PCR of human eosinophils treated with TNFα and IL-5 family cytokines, and TSLPR surface expression on eosinophils was analyzed by flow cytometry. Eosinophils were stimulated with TSLP (with and without pre-activation with TNFα and IL-3) and evaluated for release of eosinophil derived neurotoxin (EDN), phosphorylation of STAT5, and survival by trypan blue exclusion. A blocking antibody for TSLPR was used to confirm the specificity of TSLP mediated signaling on eosinophil degranulation.</p> <p>Results</p> <p>Eosinophil expression of cell surface TSLPR and TSLPR mRNA was upregulated by stimulation with TNFα and IL-3. TSLP stimulation resulted in release of EDN, phosphorylation of STAT5 as well as promotion of viability and survival. TSLP-stimulated eosinophil degranulation was inhibited by a functional blocking antibody to TSLPR. Pre-activation of eosinophils with TNFα and IL-3 promoted eosinophil degranulation at lower concentrations of TSLP stimulation.</p> <p>Conclusions</p> <p>This study demonstrates that eosinophils are activated by TSLP and that eosinophil degranulation in response to TSLP may be enhanced on exposure to cytokines present in allergic inflammation, indicating that the eosinophil has the capacity to participate in TSLP-driven allergic responses.</p> http://www.clinicalmolecularallergy.com/content/10/1/8Thymic stromal lymphopoietinEosinophilsAllergic inflammationEosinophil derived neurotoxin |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Cook Ellen B Stahl James L Schwantes Elizabeth A Fox Kristen E Mathur Sameer K |
spellingShingle |
Cook Ellen B Stahl James L Schwantes Elizabeth A Fox Kristen E Mathur Sameer K IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation Clinical and Molecular Allergy Thymic stromal lymphopoietin Eosinophils Allergic inflammation Eosinophil derived neurotoxin |
author_facet |
Cook Ellen B Stahl James L Schwantes Elizabeth A Fox Kristen E Mathur Sameer K |
author_sort |
Cook Ellen B |
title |
IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation |
title_short |
IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation |
title_full |
IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation |
title_fullStr |
IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation |
title_full_unstemmed |
IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation |
title_sort |
il-3 and tnfα increase thymic stromal lymphopoietin receptor (tslpr) expression on eosinophils and enhance tslp-stimulated degranulation |
publisher |
BMC |
series |
Clinical and Molecular Allergy |
issn |
1476-7961 |
publishDate |
2012-07-01 |
description |
<p>Abstract</p> <p>Background</p> <p>Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Therefore, we sought to determine whether TSLP could activate eosinophils, focusing on measuring the regulation of TSLPR expression on eosinophils and degranulation in response to TSLP, as well as other eosinophil activation responses.</p> <p>Methods</p> <p>Eosinophil mRNA expression of TSLPR and IL-7Rα was examined by real-time quantitative PCR of human eosinophils treated with TNFα and IL-5 family cytokines, and TSLPR surface expression on eosinophils was analyzed by flow cytometry. Eosinophils were stimulated with TSLP (with and without pre-activation with TNFα and IL-3) and evaluated for release of eosinophil derived neurotoxin (EDN), phosphorylation of STAT5, and survival by trypan blue exclusion. A blocking antibody for TSLPR was used to confirm the specificity of TSLP mediated signaling on eosinophil degranulation.</p> <p>Results</p> <p>Eosinophil expression of cell surface TSLPR and TSLPR mRNA was upregulated by stimulation with TNFα and IL-3. TSLP stimulation resulted in release of EDN, phosphorylation of STAT5 as well as promotion of viability and survival. TSLP-stimulated eosinophil degranulation was inhibited by a functional blocking antibody to TSLPR. Pre-activation of eosinophils with TNFα and IL-3 promoted eosinophil degranulation at lower concentrations of TSLP stimulation.</p> <p>Conclusions</p> <p>This study demonstrates that eosinophils are activated by TSLP and that eosinophil degranulation in response to TSLP may be enhanced on exposure to cytokines present in allergic inflammation, indicating that the eosinophil has the capacity to participate in TSLP-driven allergic responses.</p> |
topic |
Thymic stromal lymphopoietin Eosinophils Allergic inflammation Eosinophil derived neurotoxin |
url |
http://www.clinicalmolecularallergy.com/content/10/1/8 |
work_keys_str_mv |
AT cookellenb il3andtnfaincreasethymicstromallymphopoietinreceptortslprexpressiononeosinophilsandenhancetslpstimulateddegranulation AT stahljamesl il3andtnfaincreasethymicstromallymphopoietinreceptortslprexpressiononeosinophilsandenhancetslpstimulateddegranulation AT schwanteselizabetha il3andtnfaincreasethymicstromallymphopoietinreceptortslprexpressiononeosinophilsandenhancetslpstimulateddegranulation AT foxkristene il3andtnfaincreasethymicstromallymphopoietinreceptortslprexpressiononeosinophilsandenhancetslpstimulateddegranulation AT mathursameerk il3andtnfaincreasethymicstromallymphopoietinreceptortslprexpressiononeosinophilsandenhancetslpstimulateddegranulation |
_version_ |
1725196368910221312 |