SEROTONIN REGULATION OF INTERLEUKIN-1 MESSENGER-RNA IN RAT UTERINE SMOOTH-MUSCLE CELLS - RELATIONSHIP TO THE PRODUCTION OF INTERSTITIAL COLLAGENASE

Previous studies have shown that the production of interstitial collag enase by rat myometrial smooth muscle cells is dependent on serotonin. These cells fail to produce collagenase early in culture, however, an d produce the enzyme only 8-12 days after confluence. During the early quiescent period, collagenase production can be induced by low concen trations of bacterial endotoxin. Under these conditions, interleukin ( IL)-1 alpha and IL-1 beta mRNAs increase coincident with collagenase a nd collagenase mRNA. Serotonin removal decreases IL-1 alpha and IL-1 b eta mRNAs, an effect that is rapidly reversed upon readdition of serot onin. Conversely, seretonin-dependent increases in IL-1 mRNAs are bloc ked by progesterone. Experiments with 5-HT2 receptor agonists and anta gonists indicate that induction is mediated by the 5-HT2 receptor subt ype. In serotonin-treated cells late in culture, IL-1 mRNAs increase c oincident with the production of collagenase. Similarly, exogenous IL- 1 fully substitutes for lipopolysaccharide in stimulating myometrial c ells to produce collagenase early in culture. Cells treated with IL-1 receptor antagonist fail to make IL-1 mRNAs or collagenase but produce collagenase and IL-1 mRNAs following antagonist removal. These result s indicate that serotonin-dependent IL-1 production by the myometrial cell is required for collagenase production and that IL-1 participates in its own production via an autocrine mechanism.