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Ying Lu, Yang Liu, Ken Fukuda, Yoshikuni Nakamura, Naoki Kumagai, Teruo Nishida; Inhibition by Triptolide of Chemokine, Proinflammatory Cytokine, and Adhesion Molecule Expression Induced by Lipopolysaccharide in Corneal Fibroblasts. Invest. Ophthalmol. Vis. Sci. 2006;47(9):3796-3800. doi: https://doi.org/10.1167/iovs.06-0319.
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purpose. The production of proinflammatory cytokines and chemokines as well as the surface expression of intercellular adhesion molecule (ICAM)-1 by corneal fibroblasts contribute to corneal inflammation. The effects of triptolide on the expression of these proteins induced by lipopolysaccharide (LPS) in human corneal fibroblasts were examined in comparison with those of dexamethasone.
methods. The release of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, granulocyte colony–stimulating factor (G-CSF), granulocyte-macrophage colony–stimulating factor (GM-CSF), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1β, and IL-8 from cultured corneal fibroblasts was measured with assay kits. Surface expression of ICAM-1 on the cultured cells was measured with a whole-cell enzyme-linked immunosorbent assay.
results. Lipopolysaccharide (LPS) induced the release of the proinflammatory cytokine IL-6 and that of the chemokines G-CSF, MCP-1, MIP-1β, and IL-8 as well as surface expression of ICAM-1 by corneal fibroblasts, whereas IL-1β, TNF-α, and GM-CSF were not detected in the culture supernatants of cells incubated with or without LPS. Triptolide and dexamethasone each inhibited in a concentration-dependent manner the LPS-induced release of IL-6, G-CSF, MCP-1, and IL-8 by corneal fibroblasts. Whereas the inhibitory effect of dexamethasone on LPS-induced IL-6 release was greater than that of triptolide, the inhibitory effect of triptolide on LPS-induced G-CSF release was more pronounced than was that of dexamethasone. Dexamethasone also inhibited LPS-induced MIP-1β release, whereas triptolide did not. Both compounds inhibited the LPS-induced surface expression of ICAM-1.
conclusions. Triptolide inhibits the LPS-induced expression of IL-6, chemokines (G-CSF, MCP-1, IL-8), and ICAM-1 in cultured human corneal fibroblasts. This compound might thus be expected to limit the infiltration of immune cells into the cornea.
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