Elevated Intracellular cAMP Levels Inhibit Interleukin-1 Production by the Tumour Cell Line U937
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Interleukin-1 (IL-1) produced by a human tumour cell line was purified to homogeneity. Scrum-free supernatants of cultured myelomonocytic leukaemic cells. U937. which were stimulated by the exotoxin of toxic shock strains of Slaphylococcus aureus. contained high titres of lymphocyte-activating factor (LAF) activity. An acidic (pl 5.5) IL-1 was purified from these supernatants by high pressure liquid chromatography (r p.-h.p.l.c) in a series of three columns reverse phase, hydroxyapatite and gel exclusion The purified IL-1 migrated as a single molecule during SDS-PAGE analysis; LAF activity could be recovered from the 15 kD region of the gel The induction of IL-1 synthesis was examined in the macrophage. Several molecules that cause increased intracellular cAMP levels effectively inhibited the production of IL-1 from peripheral blood leucocytes. This inhibition was also seen in the U937 tumour cell, suggesting that IL-1 gene regulation may be studied in this model system.
KEY WORDS: Interleukin-1, Purification, Human tumour cell hne