title: Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells.
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.
authors.affiliation: Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Summers
authors.affiliation: Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Hammons
authors.affiliation: Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Jasbir
authors.initials: J
authors.lastname: Arora
authors.affiliation: Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Suhong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Jeanine
authors.initials: J
authors.lastname: Jochems
authors.affiliation: Centers for Cancer Pharmacology, Pharmacogenetics, and Excellence in Environmental Toxicology, Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Blair
authors.affiliation: 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: aswhiteh@exchange.upenn.edu.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Whitehead
mesh_terms: D000964:Antimetabolites, Antineoplastic; D050197:Atherosclerosis / Q000473:pathology; D001973:Bromodeoxyuridine; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005492:Folic Acid / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D005494:Folic Acid Deficiency / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008727:Methotrexate / Q000494:pharmacology*; D010641:Phenotype
chemical_list: D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D005492:Folic Acid; D001973:Bromodeoxyuridine; D008727:Methotrexate
keywords: Folate; Gene expression; Immune modulation; Inflammation; Methotrexate