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E. Delair, J. Dupouy-Camet, M.-P. Roisin; In vitro Effect of Tnf-Alpha and Inf-Gamma in Retinal Cells Infection by Toxoplasma Gondii. Invest. Ophthalmol. Vis. Sci. 2008;49(13):826.
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Toxoplasma gondii is an intracellular protozoan parasite and the most common cause of infectious posterior uveitis. Cytokines play an important role in the regulation of T.gondii infection. This study was conducted to evaluate the in vitro effect of alpha tumor necrosing factor (TNF-α) and gamma interferon (INF-γ) in rat retinal cells infection by Toxoplasma gondii.
Rat retinal cells - retinal pigment epithelial cells (RPE) and retinal Müller glial (RMG) cells - were in vitro infected by Toxoplasma gondii RH strain tachyzoïtes. Culture cells were stimulated with TNF-α, INF-γ, and LPS, alone at different concentrations, or in combination. The effect of TNF-α and INF-γ in T.gondii invasion and replication between retinal cells was evaluated by two different methods : measurement of [3H]-uracil incorporation and counting infected cells under microscopic examination. Cells nitric oxide (NO) production was also evaluated.
IFN-γ significantly inhibits [3H]-uracil incorporation in RMG and RPE cells (respectively 35 %, 83 % and 87 % inhibition at 0.1, 1 and 10 ng/ml for RMG and 0 %, 30 % and 75 % for RPE). TNF-α significantly inhibits [3H]-uracil incorporation in RPE cells (23 % and 38 % inhibition at 1 and 10 ng/ml), but not in RMG cells. NO production by both pigment epithelium cells and Müller cells increased significantly after stimulation with IFN-γ + TNF-α or IFN-γ + TNF-α + LPS combinations. Neither IFN-γ alone, nor TNF-α significantly increased NO production.
Anti-Toxoplasma activity was found with IFN-γ and TNF-α within retinal pigment epithelial cells, whereas only IFN-γ but not TNF-α inhibited T.gondii replication in retinal Müller glial cells. These inhibitor effect acted in a dose-dependent manner, and appeared independent of NO production by the cells.
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