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• W4313335967 endingPage "2843" @default.
• W4313335967 startingPage "2836" @default.
• W4313335967 abstract "Abstract Agents that increase intracellular cAMP have been shown to reduce joint inflammation in experimental arthritis, presumably by lowering the release of proinflammatory cytokines, such as TNF-α. Recent studies suggest that, in joints of patients with rheumatoid arthritis, TNF-α release from macrophages is triggered by their interaction with IL-15-stimulated T lymphocytes. In this report, we analyze the effect of rolipram, a cAMP-specific phosphodiesterase inhibitor, on TNF-α production in this experimental system. Cocultures of U937 cells with IL-15-stimulated T cells, but not control T cells, resulted in increased release of TNF-α. Pretreatment of T cells with rolipram or cAMP analogues inhibited the IL-15-stimulated increases in proliferation, expression of cell surface molecules CD69, ICAM-1, and LFA-1, and release of TNF-α from macrophages. Addition of PMA to T cells dramatically increased the expression of cell surface molecules, but had little or no effect on TNF-α release from either T cells or from cocultures, suggesting that other surface molecules must also be involved in T cell/macrophage contact-mediated production of TNF-α. Addition of PMA synergistically increased the proliferation of IL-15-stimulated T cells and the secretion of TNF-α from IL-15-stimulated T cell/macrophage cocultures. Rolipram and 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) blocked these increases. Measurement of protein kinase A (PKA) activity and the use of inhibitory cAMP analogues (RpCPT-cAMP) confirmed that rolipram worked by stimulating PKA. These data suggest that PKA-activating agents, such as rolipram, can block secretion of TNF-α from macrophages by inhibiting T cell activation and expression of surface molecules." @default.
• W4313335967 created "2023-01-06" @default.
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• W4313335967 date "1999-09-01" @default.
• W4313335967 modified "2023-10-14" @default.
• W4313335967 title "Regulation of IL-15-Stimulated TNF-α Production by Rolipram" @default.
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• W4313335967 doi "https://doi.org/10.4049/jimmunol.163.5.2836" @default.
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