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- W2079809096 abstract "Human alveolar macrophages (AM) are antigen-presenting cells that have an important immune effector function in the lung. We have previously shown that AM produce a specific interleukin-1 (IL-1) inhibitor of 20 to 25 kD that blocks biologic activities of IL-1α and IL-1β such as prostaglandin E2 production by fibroblasts. This inhibitor acts as a receptor antagonist (IL-1ra) by binding to the IL-1 receptor. We are now presenting evidence that the natural AM-derived IL-1ra is immunologically identical to IL-1ra cloned from human peripheral blood monocytes and shows a band at 20 kD compatible with the natural glycosylated IL-1ra. No constitutive expression of IL-1 mRNA was detected when analyzed by Northern blot immediately after bronchoalveolar lavage from six control patients. Comparison of in vitro kinetics of IL-1ra, IL-1α, and IL-1β analyzed during culture in the presence or absence of phorbol myristate acetate revealed that their mRNA expression was asynchronous. IL-1α and IL-1β mRNA were expressed after as little as 15 min, whereas IL-1ra mRNA was detectable only after 3 h in culture. The production of IL-1ra was measured by enzyme-linked immunosorbent assay and compared with that of IL-1α and IL-1β. In freshly isolated AM (106/ml), cell-associated IL-1ra was present in an average amount of 2.0 ± 0.5 ng/ml, i.e., 25 and 100 times more than IL-1α and IL-1β, respectively. After 24 h of culture, the amount of extracellular IL-1ra was equal to that of intracellular IL-1ra and was 30 and 100 times higher than IL-1α or IL-1β, respectively. In the presence of IL-4, a clear dissociation between IL-1α or IL-1β and IL-1ra production was observed, the production of IL-1ra being increased whereas that of IL-1α or IL-1β was decreased or unchanged. The results show that the kinetics of IL-1ra, Il-1α, and IL-1β production differ and that cytokines such as IL-4 favor the production of IL-1ra at the transcriptional level to preserve the lung from inflammation." @default.
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- W2079809096 date "1993-02-01" @default.
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- W2079809096 title "Regulation of Interleukin-1ra, Interleukin-1α, and Interleukin-1βProduction by Human Alveolar Macrophages with Phorbol Myristate Acetate, Lipopolysaccharide, and Interleukin-4" @default.
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- W2079809096 doi "https://doi.org/10.1165/ajrcmb/8.2.160" @default.
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