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V. K. Kommineni, C. N. Nagineni, B. Detrick, J. J. Hooks; Interferon- Downregulates IL-1 and TNF- Induced IL-11 Secretion by Human Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2524.
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The expression and the role of Interleukin-11 (IL-11), a pleiotropic cytokine with anti-inflammatory and cytoprotective properties, in retinal patho-physiology are not known. We evaluated the effects of various cytokines on IL-11 secretion by human retinal pigment epithelial (HRPE) cells.
Primary cell lines of HRPE, obtained from donor eyes, were treated with various cytokines in serum-free medium for 24 h. The levels of IL-11 in culture supernatant fluids were determined by ELISA. The results are means of at least 4 experiments performed with duplicate samples. IL-11 mRNA was analyzed by conventional and Real-Time PCR methods. IFN-γ signal transduction inhibitor, JAK-1, was used to delineate the mechanisms of IFN-γ effects on IL-11 expression by HRPE cells.
IL-11 secretion was not observed in untreated and IFN-γ treated HRPE cells. TNF-α induced small quantities of IL-11 while IL-6, IL-8 and MCP-1 had no effects. IL-1α and IL-1ß induced secretion of 552 and 549 pg/ml of IL-11 respectively. IL-1 and TNF-α acted synergistically to enhance IL-11 secretion. IL-1α + TNF-α and IL-1ß + TNF-α induced secretion of 2087 and 2052 pg/ml of IL-11 respectively. IFN-γ inhibited IL-1, and IL-1+TNF-α induced secretion of IL-11 by more than 70%. JAK-1 inhibitor reversed the inhibitory effects of IFN-γ on IL-11 secretion induced by IL-1, and IL-1+TNF-α significantly.
Our results show that HRPE cells secrete significant quantities of IL-11 secretion in the presence of IL-1 and TNF-α. IFN-γ inhibits IL-11 secretion induced by IL-1 and TNF-α through JAK-STAT pathways. IL-11, a known anti-inflammatory and cytoprotective cytokine, secretion by HRPE cells may prevent/reduce pathological consequences of inflammatory diseases in the retina.
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