CYTOKINE-INITIATED SIGNAL-TRANSDUCTION IN HUMAN MYOMETRIAL CELLS

PROBLEM: The objectives of this study were to evaluate interleukin-1 (IL-1) binding and some postreceptor actions of this cytokine and tumor necrosis factor (TNF) in human myometrial cells (HMC). METHOD: Monolayer cultures of HMC were used to characterize binding and to measure cyclic (c)AMP, prostaglandin (PG)E2, and PGI2 production. Membrane preparations were used to assess ADP-ribosylation and for immunoblotting. RESULTS: HMC were found to specifically bind [I-125]IL-1 with an apparent K(d) of 2 x 10(-10))M. Incubation of HMC with IL-1 or TNF caused a time-dependent and dose-dependent accumulation of cAMP, as well as a significant potentiation of forskolin-promoted cAMP production. These cytokines also increase PGE2 and PGI2 output, independently of the activation of adenylyl cyclase. IL-1 treatment had no measurable effect either on cholera toxin-mediated and pertussis toxin-mediated ADP-ribosylation, or on the amount of G(i) proteins, as assessed by immunoblotting using a polyclonal antibody. CONCLUSIONS: It is suggested that IL-1 and TNF may activate one or more isoforms of the catalytic component of adenylyl cyclase, raising intracellular cAMP.