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Naoki Kumagai, Ken Fukuda, Yoshitsugu Ishimura, Teruo Nishida; Synergistic Induction of Eotaxin Expression in Human Keratocytes by TNF-α and IL-4 or IL-13. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1448-1453.
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purpose. To investigate the effects of tumor necrosis factor (TNF)-α,
interleukin (IL)-4, and IL-13 on expression of the chemokine eotaxin by
cultured human keratocytes.
methods. Cultured human keratocytes were incubated with various combinations and
concentrations of TNF-α, IL-4, and IL-13. The concentration of
eotaxin in the culture supernatant was subsequently measured by
enzyme-linked immunosorbent assay, and the amount of eotaxin mRNA in
cell lysates was determined by reverse transcription–polymerase chain
results. Keratocytes incubated in the absence of cytokines did not release
detectable amounts of eotaxin into the culture medium. Whereas
incubation of keratocytes with TNF-α, IL-4, or IL-13 alone or with
the combination of IL-4 and IL-13 had only a small effect on eotaxin
release, exposure of the cells to TNF-α in combination with either
IL-4 or IL-13 resulted in a marked increase in eotaxin production that
was both time and dose dependent. The abundance of eotaxin mRNA in
keratocytes was also increased in a synergistic manner by incubation of
cells with TNF-α together with either IL-4 or IL-13.
conclusions. Stimulation of human keratocytes with the combination of TNF-α and
either IL-4 or IL-13 resulted in synergistic increases in both the
abundance of eotaxin mRNA and the release of eotaxin protein. This
cytokine-induced increase in eotaxin production by keratocytes may
contribute to eosinophil infiltration in inflammatory ocular diseases
such as vernal keratoconjunctivitis.
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