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A. Amadi–Obi, C.–R. Yu, R. Mahdi, I. Gery, R.N. Fariss, J.Y. Tsai, C.E. Egwuagu; IL–27 Is Constitutively Expressed in the Retina and Up–Regulated During Experimental Autoimmune Uveitis (EAU) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2919.
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IL–12 family cytokines are implicated in pathogenic mechanisms of chronic inflammatory diseases including experimental autoimmune uveitis (EAU). IL–12 family includes IL–12 (p40 and p35), IL–23 (p40 and p19) and IL–27 (EBI3 and p28) and whereas IL–12 protects from EAU, IL–23 induces autoimmune inflammation through a mechanism involving IL–17. IL–27 is a newly described member of this family and its functions are not well understood. Here, we have examined whether IL–27 is expressed in the eye and if it is involved in pathogenic mechanisms of uveitis.
For induction of EAU, Balb/c or B10R111 mice were immunized with IRBP in CFA and clinical or histological signs of EAU were evaluated 7, 14, 21 and 28 days post–immunization. Expression of p40, p35, p19, EBI3 or p28 in whole eye or retina of EAU and control mice, as well as, in human retinal pigmented epithelia (hRPE) or human Muller cells was analyzed by RT–PCR, real–time PCR or Western blot analysis.
Expression of p40, p35 or p19 transcript is not detectable in normal mouse or human retina. In contrast, EBI3 and p28 transcripts are constitutively expressed in human or mouse retina. Importantly, compared to BALB/C that does not develop EAU, EBI3 and p28 transcripts are elevated in retina of the highly susceptible B10RIII strain. Highest levels of EIB3 and p28 in retina occurs at peak EAU and expression is down–regulated following disease resolution. Interestingly, EIB3 and p28 proteins are expressed in retina and RPE cell but not Muller cell and increase significantly in RPE cell following stimulation with IFNg.
Although the exact role of IL–27 in retina remains to be elucidated, constitutive expression in a mouse strain that is highly susceptible to autoimmune disease and its marked increase during EAU or following IFNg–stimulation of RPE cells that exhibit phagocytic/APC functions, suggest that IL–27 may amplify pathogenic ocular inflammation by promoting proliferation and production of IFNg by Th1 cells in the retina. Thus, suppressing IL–27 activity may be efficacious in treatment of uveitis.
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