Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation.

Hdl Handle:
http://hdl.handle.net/10147/229194
Title:
Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation.
Authors:
Walsh, Marie-Therese; Connell, Katie; Sheahan, Anita M; Gleich, Gerald J; Costello, Richard W
Affiliation:
Department of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland. mtwalsh@rcsi.ie
Citation:
Eosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation. 2011, 45 (5):946-52 Am. J. Respir. Cell Mol. Biol.
Journal:
American journal of respiratory cell and molecular biology
Issue Date:
Nov-2011
URI:
http://hdl.handle.net/10147/229194
DOI:
10.1165/rcmb.2010-0454OC
PubMed ID:
21454806
Abstract:
Eosinophils exert many of their inflammatory effects in allergic disorders through the degranulation and release of intracellular mediators, including a set of cationic granule proteins that include eosinophil peroxidase. Studies suggest that eosinophils are involved in remodeling. In previous studies, we showed that eosinophil granule proteins activate mitogen-activated protein kinase signaling. In this study, we investigated the receptor mediating eosinophil peroxidase-induced signaling and downstream effects. Human cholinergic neuroblastoma IMR32 and murine melanoma B16.F10 cultures, real-time polymerase chain reaction, immunoprecipitations, and Western blotting were used in the study. We showed that eosinophil peroxidase caused a sustained increase in both the expression of epidermal growth factor-2 (HER2) and its phosphorylation at tyrosine 1248, with the consequent activation of extracellular-regulated kinase 1/2. This, in turn, promoted a focal adhesion kinase-dependent egress of the cyclin-dependent kinase inhibitor p27(kip) from the nucleus to the cytoplasm. Eosinophil peroxidase induced a HER2-dependent up-regulation of cell proliferation, indicated by an up-regulation of the nuclear proliferation marker Ki67. This study identifies HER2 as a novel mediator of eosinophil peroxidase signaling. The results show that eosinophil peroxidase, at noncytotoxic levels, can drive cell-cycle progression and proliferation, and contribute to tissue remodeling and cell turnover in airway disease. Because eosinophils are a feature of many cancers, these findings also suggest a role for eosinophils in tumorigenesis.
Item Type:
Article
Language:
en
MeSH:
Active Transport, Cell Nucleus; Animals; Cell Line; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p27; Eosinophil Peroxidase; Eosinophils; Epidermal Growth Factor; Focal Adhesion Protein-Tyrosine Kinases; Humans; MAP Kinase Signaling System; Mice; Phosphorylation; Receptor, erbB-2
ISSN:
1535-4989

Full metadata record

DC FieldValue Language
dc.contributor.authorWalsh, Marie-Thereseen_GB
dc.contributor.authorConnell, Katieen_GB
dc.contributor.authorSheahan, Anita Men_GB
dc.contributor.authorGleich, Gerald Jen_GB
dc.contributor.authorCostello, Richard Wen_GB
dc.date.accessioned2012-06-15T15:30:36Z-
dc.date.available2012-06-15T15:30:36Z-
dc.date.issued2011-11-
dc.identifier.citationEosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation. 2011, 45 (5):946-52 Am. J. Respir. Cell Mol. Biol.en_GB
dc.identifier.issn1535-4989-
dc.identifier.pmid21454806-
dc.identifier.doi10.1165/rcmb.2010-0454OC-
dc.identifier.urihttp://hdl.handle.net/10147/229194-
dc.description.abstractEosinophils exert many of their inflammatory effects in allergic disorders through the degranulation and release of intracellular mediators, including a set of cationic granule proteins that include eosinophil peroxidase. Studies suggest that eosinophils are involved in remodeling. In previous studies, we showed that eosinophil granule proteins activate mitogen-activated protein kinase signaling. In this study, we investigated the receptor mediating eosinophil peroxidase-induced signaling and downstream effects. Human cholinergic neuroblastoma IMR32 and murine melanoma B16.F10 cultures, real-time polymerase chain reaction, immunoprecipitations, and Western blotting were used in the study. We showed that eosinophil peroxidase caused a sustained increase in both the expression of epidermal growth factor-2 (HER2) and its phosphorylation at tyrosine 1248, with the consequent activation of extracellular-regulated kinase 1/2. This, in turn, promoted a focal adhesion kinase-dependent egress of the cyclin-dependent kinase inhibitor p27(kip) from the nucleus to the cytoplasm. Eosinophil peroxidase induced a HER2-dependent up-regulation of cell proliferation, indicated by an up-regulation of the nuclear proliferation marker Ki67. This study identifies HER2 as a novel mediator of eosinophil peroxidase signaling. The results show that eosinophil peroxidase, at noncytotoxic levels, can drive cell-cycle progression and proliferation, and contribute to tissue remodeling and cell turnover in airway disease. Because eosinophils are a feature of many cancers, these findings also suggest a role for eosinophils in tumorigenesis.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to American journal of respiratory cell and molecular biologyen_GB
dc.subject.meshActive Transport, Cell Nucleus-
dc.subject.meshAnimals-
dc.subject.meshCell Line-
dc.subject.meshCell Proliferation-
dc.subject.meshCyclin-Dependent Kinase Inhibitor p27-
dc.subject.meshEosinophil Peroxidase-
dc.subject.meshEosinophils-
dc.subject.meshEpidermal Growth Factor-
dc.subject.meshFocal Adhesion Protein-Tyrosine Kinases-
dc.subject.meshHumans-
dc.subject.meshMAP Kinase Signaling System-
dc.subject.meshMice-
dc.subject.meshPhosphorylation-
dc.subject.meshReceptor, erbB-2-
dc.titleEosinophil peroxidase signals via epidermal growth factor-2 to induce cell proliferation.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Dublin, Ireland. mtwalsh@rcsi.ieen_GB
dc.identifier.journalAmerican journal of respiratory cell and molecular biologyen_GB
dc.description.provinceLeinsteren
All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.