Gene expression changes in lymphoblastoid cell lines and primary B cells by dexamethasone

Background Human Epstein-Barr virus-transformed lymphoblastoid cell lines (LCLs) have been thought to be a useful model system for pharmacogenomics studies. The purpose of this study was to determine the effect of Epstein-Barr virus transformation on gene expression changes by dexamethasone (Dex) in LCLs and primary B cells (PBCs) derived from the same individuals. Patients and methods We prepared LCLs and purified PBCs from the same six male donors participating in the Childhood Asthma Management Program clinical trial, and compared mRNA profiles after 6 h incubation with Dex (10−6 mol/l) or sham buffer. We assessed differential expression and put the list of differentially expressed genes into the web interface of ConsensusPathDB to find the pathway-level interpretation of our genes specified. As a supplementary analysis, we looked at the expression of the Dex-regulated (inducing or repressing) genes in treatment-naive PBCs and LCLs (pre-Dex treatment) from the GSE30916 dataset. Results By hierarchical clustering, we found clustering of probes by cell types but not by individuals irrespective of Dex treatment. We observed that the Dex-regulated genes significantly overlapped in PBCs and LCLs. In addition, the expression of these genes showed significant correlations between treatment-naive PBCs and LCLs. Common genes showing significantly decreased expressions by the Dex treatment in both cells were enriched in immune responses and proinflammatory signaling pathways. Conclusion Taken together, these results suggest the uses of LCLs are representative of the primary biologic effects of corticosteroids treatment. Correspondence to Kelan G. Tantisira, MD, MPH, Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA Tel: +1 617 525 0863; fax: +1 617 525 0958; e-mail: kelan.tantisira@channing.harvard.edu Received July 13, 2018 Accepted November 25, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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