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Richard D. Dix, Emily L. Blalock, Courtney L. Meier-Jewett, Christine I. Alston, Hsin Chien; SOCS1 and SOCS3 mRNAs Are Upregulated Intraocularly During Progression of Experimental Cytomegalovirus Retinitis in Mice with Retrovirus-induced Immunosuppression. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2966.
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SOCS (suppressor of cytokine signaling) proteins are key regulators of innate and adaptive immunity. Of these, SOCS1 is an inhibitor of interferon signaling and SOCS3 regulates the divergent actions of IL-6 and IL-10. We therefore hypothesized that SOCS1 and/or SOCS3 are upregulated during progression of experimental murine cytomegalovirus (MCMV)-induced retinitis in mice with retrovirus-induced immunosuppression.
C57BL/6 mice with MAIDS of 10-weeks duration were inoculated subretinally with MCMV or mock-injected. At 3, 6, and 10 days postinfection, whole MCMV-infected and mock-injected eyes were collected from all animals and subjected to real time RT-PCR assay for quantification of SOCS1 and SOCS3 mRNAs.
When compared with mock-injected eyes, MCMV-infected eyes of mice with MAIDS exhibited a 1.8-fold, 8.0-fold, and 2.1-fold increase in SOCS1 mRNA at 3, 6, and 10 days postinfection, respectively, during progression of MCMV retinitis. A similar pattern but more dramatic increase in SOCS3 mRNA was also observed during progression of retinitis in MCMV-infected eyes. When compared with mock-injected eyes, MCMV-infected mice with MAIDS exhibited a 10.4-fold, 60.6-fold, and 2.1-fold increase in SOCS3 mRNA at 3, 6, and 10 days postinfection, respectively.
MCMV subretinal inoculation of eyes of mice with MAIDS resulted in increased intraocular levels of SOCS1 and SOCS3 mRNAs that peaked by day 6 postinfection but decreased to near baseline amounts by day 10 postinfection. In comparison, intraocular levels of SOCS3 mRNA were found to be dramatically higher than intraocular levels of SOCS1 mRNA. Peak production of both SOCS1 and SOCS3 mRNAs at day 6 postinfection preceded the appearance of retinal necrosis at day 10 postinfection. SOCS1 and SOCS3 proteins may therefore play important roles in the pathogenesis of MAIDS-related MCMV retinitis.
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