title: Corticosteroids inhibit anti-IgE activities of specialized proresolving mediators on B cells from asthma patients.
abstract: Specialized proresolving mediators (SPMs) promote the resolution of inflammation and exert beneficial effects in animal models of chronic inflammatory diseases, including asthma. Previously, we have shown that certain SPMs reduce IgE production in B cells from healthy individuals, which has a critical role in allergic asthma. Here, we investigated the effects of SPMs on B cell IgE production in asthma patients. Peripheral blood mononuclear cells from asthma patients were treated with 17-HDHA or RvD1, and IgE levels were measured. RvD1 and 17-HDHA dampened IgE production in B cells from most asthma patients, whereas B cells from a subset of patients taking oral steroids were refractory to SPM treatment. Molecular mechanisms underlying the interaction between corticosteroids and SPMs were investigated by treating B cells from nonasthmatic donors with corticosteroids in vitro. Corticosteroids blocked the inhibitory effects of 17-HDHA and RvD1 on B cell IgE production by abolishing the suppressive activity of these mediators on IgE class switching. Corticosteroids decreased the expression of transcriptional repressor Bcl-6 as well as its suppressive activity on epsilon germline transcription. We conclude that 17-HDHA and RvD1 can reduce IgE production in asthma patients not taking high doses of steroids but that corticosteroids interfere with the ability of B cells to respond to proresolving mediators.
authors.affiliation: Department of Microbiology and Immunology.
authors.forename: Nina
authors.initials: N
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, and.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Thatcher
authors.affiliation: Division of Pulmonary and Critical Care Medicine, and.|Department of Environmental Medicine, University of Rochester, Rochester, New York, USA.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Sime
authors.affiliation: Department of Microbiology and Immunology.|Department of Environmental Medicine, University of Rochester, Rochester, New York, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D000305:Adrenal Cortex Hormones; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D007073:Immunoglobulin E; C062894:17-hydroxy-4,7,10,13,15,19-docosahexaenoic acid