Serotonin regulation of interleukin-1 messenger RNA in rat uterine smooth muscle cells. Relationship to the production of interstitial collagenase.

Abstract

Previous studies have shown that the production of interstitial collagenase by rat myometrial smooth muscle cells is dependent on serotonin. These cells fail to produce collagenase early in culture, however, and produce the enzyme only 8-12 days after confluence. During the early quiescent period, collagenase production can be induced by low concentrations of bacterial endotoxin. Under these conditions, interleukin (IL)-1 alpha and IL-1 beta mRNAs increase coincident with collagenase and collagenase mRNA. Serotonin removal decreases IL-1 alpha and IL-1 beta mRNAs, and effect that is rapidly reversed upon readdition of serotonin. Conversely, serotonin-dependent increases in IL-1 mRNAs are blocked by progesterone. Experiments with 5-HT2 receptor agonists and antagonists indicate that induction is mediated by the 5-HT2 receptor subtype. In serotonin-treated cells late in culture, IL-1 mRNAs increase coincident with the production of collagenase. Similarly, exogenous IL-1 fully substitutes for lipopolysaccharide in stimulating myometrial cells 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 results 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.