Transcriptional regulation of fibroblast collagen synthesis by activated mononuclear cell supernatants.

Mononuclear cells elaborate effector substances which regulate growth and synthetic activities of fibroblasts. We have studied the mechanism by which activated mononuclear cell supernatants inhibit collagen production. Activated supernatants were prepared by culturing human peripheral mononuclear cells with phytohemagglutinin. Human fibroblasts were exposed to the activated supernatants and total cellular RNA was isolated. Collagen mRNA levels were measured using a pro alpha [I] probe and poly(A+) mRNA was assayed using polyuridylic acid as the probe. Collagen production was measured as collagenase-digestible radioactivity. The results showed that pro alpha 1 [I] mRNA levels were decreased in cells incubated with the activated mononuclear cell supernatants and that the decrease was dose and time dependent. The reduction in the pro alpha 1 [I] mRNA correlated with the decrease in collagen production. No inhibition in the poly(A+) message was observed. We conclude that inhibition of collagen production by activated mononuclear cell supernatant occurs primarily at the transcriptional level and that the inhibition may be selective to collagen.