title: Eosinophil peroxidase induces expression of cholinergic genes via cell surface neural interactions.
abstract: Eosinophils localize to and release their granule proteins in close association with nerves in patients with asthma and rhinitis. These conditions are associated with increased neural function. In this study the effect of the individual granule proteins on cholinergic neurotransmitter expression was investigated. Eosinophil peroxidase (EPO) upregulated choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) gene expression. Fluorescently labeled EPO was seen to bind to the IMR-32 cell surface. Both Poly-L-Glutamate (PLG) and Heparinase-1 reversed the up-regulatory effect of EPO on ChAT and VAChT expression and prevented EPO adhesion to the cell surface. Poly-L-arginine (PLA) had no effect on expression of either gene, suggesting that charge is necessary but insufficient to alter gene expression. EPO induced its effects via the activation of NF-κB. MEK inhibition led to reversal of all up-regulatory effects of EPO. These data indicate a preferential role of EPO signaling via a specific surface receptor that leads to neural plasticity.
authors.affiliation: Department of Medicine, Royal College of Surgeons in Ireland, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland. Electronic address: nba00@hotmail.com.
authors.forename: Nadim
authors.initials: N
authors.lastname: Akasheh
authors.affiliation: Department of Medicine, Royal College of Surgeons in Ireland, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Walsh
authors.affiliation: Department of Medicine, Royal College of Surgeons in Ireland, Smurfit Building, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Costello
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D018678:Cholinergic Agents / Q000378:metabolism; D047209:Eosinophil Peroxidase / Q000494:pharmacology / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D014407:Tumor Cells, Cultured; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018678:Cholinergic Agents; D006025:Glycosaminoglycans; D016328:NF-kappa B; D050494:Vesicular Acetylcholine Transport Proteins; D047209:Eosinophil Peroxidase; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
keywords: Cholinergic genes; Eosinophil granule proteins; Eosinophil peroxidise; Neural interaction