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Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells.

Authors
  • Summers, Carolyn M1
  • Hammons, Andrea L1
  • Arora, Jasbir1
  • Zhang, Suhong1
  • Jochems, Jeanine1
  • Blair, Ian A1
  • Whitehead, Alexander S2
  • 1 Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. , (United States)
  • 2 Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: [email protected] , (United States)
Type
Published Article
Journal
European journal of pharmacology
Publication Date
Jun 05, 2014
Volume
732
Pages
60–67
Identifiers
DOI: 10.1016/j.ejphar.2014.03.004
PMID: 24657277
Source
Medline
Keywords
License
Unknown

Abstract

EA.hy 926 cells grown under low folate conditions adopt a "pro-atherosclerotic" morphology and biochemical phenotype. Pharmacologically relevant doses of the antifolate drug methotrexate (MTX) were applied to EA.hy 926 cells maintained in normal (Hi) and low (Lo) folate culture media. Under both folate conditions, MTX caused inhibition of cell proliferation without significantly compromising metabolic activity. MTX treated Hi cells were depleted of folate derivatives, which were present in altered proportions relative to untreated cells. Transcript profiling using microarrays indicated that MTX treatment modified the transciptome in similar ways for both Hi and Lo cells. Many inflammation-related genes, most prominently those encoding C3 and IL-8, were up-regulated, whereas many genes involved in cell division were down-regulated. The results for C3 and IL-8 were confirmed by quantitative RT-PCR and ELISA. MTX appears to modify the inflammatory potential of EA.hy 926 cells such that its therapeutic properties may, at least under some conditions, be accompanied by the induction of a subset of gene products that promote and/or maintain comorbid pathologies.

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