Abstract | PURPOSE: METHODS:
RNA was isolated from human retinal microvascular endothelial cells treated with a vehicle, TNFα, or TNFα plus GSK0660. RNA-seq was performed with a 50 bp single read protocol. The differential expression was determined using edgeR and gene ontology, and a pathway analysis was performed using DAVID. RNA-seq validation was performed using qRT-PCR using the primers for ANGPTL4, CCL8, NOV, CXCL10, and PDPK1. RESULTS: TNFα differentially regulated 1,830 transcripts, many of which are involved in the cytokine- cytokine receptor interaction, chemokine signaling, and inflammatory response. Additionally, TNFα highly upregulated genes involved in leukocyte recruitment, including CCL5, CX3CL1, and CXCL10. GSK0660 differentially regulated 273 transcripts in TNFα-treated cells compared to TNFα alone. A pathway analysis revealed the enrichment of cytokine- cytokine receptor signaling. In particular, GSK0660 blocks the TNFα-induced upregulation of CCL8, a chemokine involved in leukocyte recruitment. CONCLUSIONS:
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Authors | Sara R Savage, Gary W McCollum, Rong Yang, John S Penn |
Journal | Molecular vision
(Mol Vis)
Vol. 21
Pg. 568-76
( 2015)
ISSN: 1090-0535 [Electronic] United States |
PMID | 26015769
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- CCL8 protein, human
- Chemokine CCL8
- Cytokines
- GSK0660
- PPAR delta
- PPAR-beta
- Sulfones
- TNF protein, human
- Thiophenes
- Tumor Necrosis Factor-alpha
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Topics |
- Cells, Cultured
- Chemokine CCL8
(genetics, metabolism)
- Cytokines
(genetics, metabolism)
- Endothelial Cells
(cytology, drug effects, metabolism)
- Gene Expression Regulation
(drug effects)
- Humans
- PPAR delta
(agonists, antagonists & inhibitors)
- PPAR-beta
(agonists, antagonists & inhibitors)
- Retinal Vessels
(cytology, drug effects, metabolism)
- Sequence Analysis, RNA
- Signal Transduction
(drug effects)
- Sulfones
(pharmacology)
- Thiophenes
(pharmacology)
- Tumor Necrosis Factor-alpha
(metabolism, pharmacology)
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