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C.N. Nagineni, V. Kutty, B. Detrick, J.J. Hooks; Expression of Transforming Growth Factor–ß1and ß2 by Human Retinal Pigment epithelial cells: Differential regulation by IFN– . Invest. Ophthalmol. Vis. Sci. 2004;45(13):628.
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Purpose:Retinal pigment epithelium (RPE) plays a vital role in the inflammatory diseases of the retina and the choroid. TGF–ß has been shown to be involved in various ocular pathophysiological and immunoregulatory activities. Therefore, we have studied the role of the inflammatory cytokines, IFN–γ, TNF– α and IL–1ß on the expression of TGF–ß in human RPE cells (HRPE). Methods:HRPE cultures were prepared from human donor eyes. Confluent cultures were serum starved for 24 h and treated with various agents for 48 h in serum free medium. The levels of total (acid activated) and mature (native) TGF–ß1 and TGF–ß2, in the culture supernatants, were determined by ELISA. Total RNA prepared from cultures treated with agents for 12 or 24 h were used for the determination of TGF–ß mRNA levels by RT–PCR.Results:TNF–α and IL–1ß increased the mRNA levels of both TGF–ß1 and TGF–ß2. IFN–γ enhanced TGF–ß1 mRNA levels but decreased TGF–ß2 mRNA. IFN–γ also decreased TGF–ß2 mRNA levels elevated by TNF–α and IL–1ß. Secretion of TGF–ß1 and TGF–ß2 protein by HRPE was evaluated to determine whether changes in mRNA levels affect protein synthesis. HRPE cells secreted TGF–ß1 in a latent form while 10–40 % of the secreted TGF–ß2 is in a mature form. IFN–γ enhanced TGF–ß1 but inhibited TGF–ß2 secretion significantly in a dose dependent manner. IFN–γ further enhanced the secretion of TGF–ß1 induced by TNF–α or IL–1ß while inhibiting the TNF–α or IL–1ß induced secretion of TGF–ß2. Conclusions:The contrasting effects of IFN–γ on TGF–ß1 and TGF–ß2 expression strongly indicate differential roles for TGF–ß1 and TGF–ß2 in the inflammatory diseases of the retina and choroid.
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