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H. Takase, C.R. Yu, B.P. Vistica, D.I. Ham, E.F. Wawrousek, C.E. Egwuagu, I. Gery; Variability in the Profiles of Gene Expression Among Different Models of Ocular Inflammation . Invest. Ophthalmol. Vis. Sci. 2005;46(13):987.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: TCR engagement, followed by T–cell activation and cytokine release, is the major mechanism that triggers the pathogenic process of immune–mediated inflammation such as in experimental autoimmune uveitis (EAU). Inflammatory changes also develop, however, in eyes of transgenic mice in which interleukin (IL)–1 or IL–7 are expressed transgenically. Here, we compared the profile of gene expression of inflammation–related molecules in eyes with inflammation induced by TCR engagement (EAU) or transgenic (Tg) expression of cytokines. Methods: Eyes from transgenic (Tg) mice expressing IL–1, IL–7, or interferon–gamma (IFN–γ) under control of the alpha A–crystallin promoter, were collected at 4 to 8 weeks of age, while eyes with EAU were obtained from B10.RIII mice, 14 days following immunization with IRBP peptide 161–180. Total RNA was extracted from whole eyeball or lens, and mRNA expression of 10 cytokines, 10 chemokines, 9 chemokine receptors, 9 adhesion molecules, and 2 transcription factors were tested by real–time PCR analysis and RNase protection assay. Results: Major observations: (i) Unlike the bias toward Th1 response in eyes with EAU, eyes of IL–1 and IL–7 Tg mice exhibited similar levels of upregulation of cytokines, chemokines, chemokine receptors and transcription factors that characterize both Th1– and Th2– type immune responses; (ii) in general, the levels of upregulation of all tested families of molecules were higher in eyes of IL–1 Tg mice than in those of IL–7 Tg animals; (iii) Eyes of IFN–γ Tg mice, did not develop any significant inflammation and, with the exception of IFN–γ, showed minimal or no upregulation of the tested inflammation–related molecules. Conclusions: Upregulation of most inflammation–related molecules is observed in mouse eyes in which inflammatory changes are induced by Tg expression of IL–1 or IL–7. Yet, remarkable quantitative differences were found between the expression profile in these Tg mice and mice with EAU, in which the pathogenic process is TCR–initiated.
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