Fibroblast interleukin 1 beta: synergistic stimulation by recombinant interleukin 1 and tumor necrosis factor and posttranscriptional regulation.

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Abstract
To understand the role fibroblasts play in mediating and amplifying the effects of inflammatory cytokines, we determined whether recombinant interleukin 1 (IL-1) and recombinant tumor necrosis factor (TNF), alone and in combination, stimulated fibroblasts to produce IL-1.beta.. Recombinant IL-1 (.alpha. and .beta.) stimulated fibroblast IL-1.beta. mRNA accumulation, whereas recombinant TNF did not. In addition, simultaneous stimulation with recombinant IL-1 (.alpha. or .beta.) and recombinant TNF resulted in a synergistic increase in IL-1.beta. mRNA levels. However, in all cases, IL-1.beta. mRNA accumulation was not associated with fibroblast production of soluble IL-1.beta. protein. Lysates of unstimulated, recombinant IL-1-stimulated, and recombinant TNF-stimulated fibroblasts did not contain IL-1.beta. prohormone. In contrast, IL-1.beta. prohormone was detected in lysates of fibroblasts incubated simultaneously with recombinant IL-1 and recombinant TNF. These studies demonstrate that recombinant IL-1 stimulates fibroblast IL-1.beta. mRNA accumulation and that recombinant IL-1 and recombinant TNF synergize to further up-regulate IL-1.beta. mRNA levels. In addition, they show that IL-1.beta. production by human lung fibroblasts is inhibited at a posttranscriptional level. Translational control appears to be important in recombinant IL-1-stimulated fibroblasts and posttranslational control is important in fibroblasts stimulated simulataneously with recombinant IL-1 and recombinant TNF.