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Ayako Yoshida, Susan G. Elner, Zong-Mei Bian, Steven L. Kunkel, Nicholas W. Lukacs, Victor M. Elner; Differential Chemokine Regulation by Th2 Cytokines during Human RPE–Monocyte Coculture. Invest. Ophthalmol. Vis. Sci. 2001;42(7):1631-1638.
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purpose. To determine the effects of the potent anti-inflammatory Th2 cytokines,
interleukin (IL)-4, -10, and -13, on IL-8 and monocyte
chemoattractant protein (MCP) 1 production by human retinal pigment
epithelial (HRPE) cells, monocytes, and HRPE cell–monocyte cocultures.
methods. Enzyme-linked immunosorbent assays were performed to determine IL-8 and
MCP-1 secretion by HRPE cells, monocytes, and HRPE cell–monocyte
cocultures stimulated with IL-1β or TNF-α, either alone, or in
combination with IL-4, -10, or -13, at various time points.
results. IL-4 and -13, but not IL-10, enhanced constitutive and TNF-α–induced
HRPE IL-8 and MCP-1 secretion. IL-4 also enhanced IL-1β–induced HRPE
IL-8. IL-4 and -13 reduced monocyte IL-8 and MCP-1, whereas IL-10
reduced monocyte IL-8 but enhanced MCP-1. Overlay of monocytes onto
HRPE cell cultures resulted in increased IL-8 and MCP-1 secretion. IL-8
secretion by HRPE cell–monocyte cocultures was inhibited by IL-4, -10,
and -13, whereas MCP-1 was inhibited only by IL-10. These cytokines
also inhibited IL-1β potentiation of IL-8, but not MCP-1 secretion by
cocultures. IL-4 enhanced TNF-α potentiation of chemokine secretion
by cocultures, whereas IL-10 had no effects. IL-13 potentiated
TNF-α–induced MCP-1, but not IL-8 secretion by cocultures.
conclusions. IL-4, -10 and -13 have complex effects on chemokine secretion by HRPE
cells, monocytes, and HRPE cell–monocyte cocultures. IL-10 appears to
be the most consistently suppressive cytokine, suggesting potential
therapeutic usefulness of IL-10 in the treatment of ocular inflammatory
and proliferative diseases.
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