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Corticosteroid modulation of immunoglobulin expression and B cell function in COPD

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Title: Corticosteroid modulation of immunoglobulin expression and B cell function in COPD
Authors: Lee, J
Machin, M
Russell, KE
Pavlidis, S
Zhu, J
Barnes, PJ
Chung, KF
Adcock, IM
Durham, AL
Item Type: Journal Article
Abstract: Purpose: To investigate changes in gene expression that occur in COPD following corticosteroid treatment and identify the mechanisms that regulate these changes. Procedures: Biopsies were taken from COPD patients (GOLD stage I-II) before and after treatment fluticasone propionate (FP)/salmeterol (SM) (Seretide┬« 50/500, 4 weeks). Gene expression was measured by microarray, confirmed by RT-qPCR. The effect of FP on IgG expression and B-cell proliferation in the presence of oxidative stress was also studied. Findings: FP/SM significantly increased the expression of 180 genes whilst repressing 343 genes. The top 5 down-regulated genes were associated with immunoglobulin production, whereas the immunomodulatory FK506 binding protein (FK506BP) was up-regulated. Genes including IL6, IL8 and the TBET encoding TBX21 were unaffected. FP reduced IgG protein and mRNA expression and proliferation of human B cells through the dephosporylation of ERK1/2 via increased DUSP1 expression. Consistent with in vivo data, oxidative stress did not prevent FP-induced suppression of IgG expression in human B-cells in vitro. Controls: Changes in expression were validated using qPCR and by gene set enrichment analysis in distinct COPD cohorts. Conclusions: FP may reduce the adaptive immune response in COPD and may be more effective in patients with an increased B cell/antibody response indicated by high autoantibody titres.
Issue Date: 1-May-2016
Date of Acceptance: 27-Jan-2016
URI: http://hdl.handle.net/10044/1/29461
DOI: 10.1096/fj.201500135
ISSN: 0892-6638
Publisher: Federation of American Society of Experimental Biology (FASEB)
Start Page: 2014
End Page: 2026
Journal / Book Title: Faseb Journal
Volume: 30
Issue: 5
Sponsor/Funder: Wellcome Trust
Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: 093080/Z/10/Z
G1000758
G1000758
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Cell Biology
Life Sciences & Biomedicine - Other Topics
DUSP1
ERK
fluticasone propionate
LABA
OBSTRUCTIVE PULMONARY-DISEASE
DUAL-SPECIFICITY PHOSPHATASES
AIRWAY GENE-EXPRESSION
MAP KINASE
INHALED FLUTICASONE
LUNG-FUNCTION
GLUCOCORTICOIDS
EXACERBATIONS
TRANSCRIPTION
INFLAMMATION
DUSP1
ERK
LABA
fluticasone propionate
Adult
Aged
B-Lymphocytes
Bronchodilator Agents
Cell Line
Cell Proliferation
Female
Fluticasone-Salmeterol Drug Combination
Gene Expression Regulation
Glucocorticoids
Humans
Immunoglobulins
Intracellular Signaling Peptides and Proteins
Male
Middle Aged
Oxidative Stress
Pilot Projects
Pulmonary Disease, Chronic Obstructive
Transcriptome
B-Lymphocytes
Cell Line
Humans
Pulmonary Disease, Chronic Obstructive
Intracellular Signaling Peptides and Proteins
Immunoglobulins
Bronchodilator Agents
Glucocorticoids
Pilot Projects
Cell Proliferation
Gene Expression Regulation
Oxidative Stress
Adult
Aged
Middle Aged
Female
Male
Transcriptome
Fluticasone Propionate, Salmeterol Xinafoate Drug Combination
0601 Biochemistry and Cell Biology
0606 Physiology
1116 Medical Physiology
Biochemistry & Molecular Biology
Publication Status: Published
Online Publication Date: 2016-02-17
Appears in Collections:Department of Surgery and Cancer
National Heart and Lung Institute
Faculty of Medicine



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