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Differential Expression of Inflammatory Cytokines and Chemokines Genes by Homocysteine in the Human Retinal Pigmented Epithelial Cells
Author(s) -
Singh Mahavir,
Olson Paul,
Grossi Federico,
Zhang Zhouning,
Tyagi Neetu,
Moshal Karni S,
Tyagi Suresh C
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a719-b
Subject(s) - pathogenesis , inflammation , chemokine , cytokine , receptor , immunology , macular degeneration , proinflammatory cytokine , biology , medicine , genetics , ophthalmology
Age related macular degeneration (AMD) is the leading cause of irreversible vision loss and blindness. It is a complex disease whose molecular basis of pathogenesis is poorly understood. Many studies have elucidated the risk factors associated with macular degeneration. However, the molecular mechanisms underlying these pathologies are not yet known. Plasma homocysteine (Hcy), a sulfur‐containing amino acid formed during the metabolism of methionine is an independent risk factor for inflammation and cardiovascular diseases and is elevated in individuals with AMD. Further, the low grade chronic inflammation is now recognized to play a pivotal role in the pathogenesis of numerous degenerative diseases, including atherosclerosis and Alzheimer’s. To test the hypothesis that Hcy causes inflammation and in part contributes to AMD, the ARPE‐19 cells were cultured in presence of various concentrations of Hcy to identify the target gene candidates. Labeled cRNAs made from the total RNA of ARPE‐19 cells were hybridized to the human inflammatory cytokines and receptor micro‐arrays. A number of genes that were both up‐regulated and down‐regulated were identified. The target genes identified through this approach fall within the categories of chemokines and cytokines, chemokines and cytokine receptors, interleukins receptors, TNF ligands and their receptors. The study supports the role of Hcy induced inflammatory genes in the pathogenesis of AMD.