Cytokine‐Initiated Signal Transduction in Human Myometrial Cells

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Abstract
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 [125I]IL‐1 with an apparent Kd of 2 × 10−10M. 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‐ribosylatidn, or on the amount of Gi 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.