Gene expression changes in lymphoblastoid cell lines and primary B cells by dexamethasone. Issue 3 (April 2019)

• Record Type: Journal Article
• Authors: Park, Heung-Woo; Dahlin, Amber; Qiu, Weiliang; Tantisira, Kelan G.
• Is Part Of: Pharmaocogenetics and genomics. Volume 29:Issue 3(2019)
• Publication Date: 2019-04
• Subjects: B cell -- gene expression -- lymphoblastoid cell lines -- steroid; Pharmacogenetics -- Periodicals; Pharmacogenomics -- Periodicals; Genetic toxicology -- Periodicals; Biomedical genetics -- Periodicals; 615.7
• DOI: 10.1097/FPC.0000000000000365
• Languages: English
• ISSNs: 1744-6872

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is available in the text.