Effects of Cytokines on Glutamate Transport in Human and Rabbit Lens Cells

Abstract

Abstract: : Extracellular glutamate (Glu) is utilized by the lens epithelium in the synthesis of lenticular glutathione (GSH). Purpose: We investigated the influence of interferons (IFN) and tumor necrosis factor-α (TNF-α) on Glu uptake activity in SV40 transformed human and rabbit lens epithelial cells. Methods: Cultures of human and rabbit lens epithelium cells were treated with natural and/or recombinant human IFN-α, IFN-ß, IFN-γ and TNF-α. The antiviral activity and uptake of radiolabeled L-Glu and D-aspartate (D-Asp) were determined. Results: Human and rabbit lens cells were equally sensitive to the antiviral activity of natural and recombinant IFN-α subtypes A, B, C, D, E, F, G, H, J, K, M, P, R, S, and T, IFN-ß, and TNF-α. Rabbit lens cells were not sensitive to the antiviral activity of human IFN-γ. The uptake of [₃H]-D-Asp (i.e., by XAG transporters) in human and rabbit lens cells was decreased by natural and/or recombinant IFNs and TNF-α, but not in rabbit lens cells by IFN-ß. IFN-α, IFN-ß, and IFN-ß inhibited [₁₄C]-L-Glu (XAG and Xc transporters) uptake in human lens cells in a dose-dependent manner. Also, IFN-α inhibited Na₊-independent uptake of [₁₄C]-L-Glu (Xc transport). Conclusions: These findings suggest that IFNs and TNF-α can inhibit the uptake of extracellular Asp and Glu by the lens XAG and Xc transporter systems. Thus, our results support the idea that inflammation-induced changes in lens metabolism and cataract formation could be due in part to inhibition of Glu uptake needed for energy and GSH synthesis.

Keywords: 437 inflammation • 321 antioxidants • 380 cytokines/chemokines