Modulation by recombinant interleukin 1 of synthesis of types I and III collagens and associated procollagen mRNA levels in cultured human cells.

Interleukin 1 (IL-1), a monocyte product, exerts a range of biological effects on nonimmune cells such as fibroblasts and chondrocytes including stimulation of synthesis and release of prostaglandin E2 (PGE2) and collagenase. We have previously shown that crude mononuclear cell-conditioned medium, which contains IL-1, also stimulates synthesis of types I and III collagens by human synovial and dermal fibroblasts and chondrocytes when the formation of PGE2, which inhibits collagen synthesis, is blocked by indomethacin. To determine whether IL-1 is responsible for the affects observed using crude monocyte-conditioned medium patterns of collagen synthesis in the three types of human cells in response to recombinant preparations of IL-1 were compared. Preincubation of chondrocytes or synovial fibroblasts with either murine (m)IL-1 alpha or human (h)IL-1 beta alone decreased synthesis of type I collagen and fibronectin. In contrast, when endogenous IL-1-stimulated PGE2 synthesis was blocked by indomethacin, an enhancing effect of IL-1 on synthesis of these matrix proteins was unmasked. The synthesis of type III collagen was enhanced by IL-1 to a greater extent than that of type I collagen in the presence of indomethacin. In human foreskin fibroblasts, which produced low levels of PGE2 even in the presence of IL-1, synthesis of types I and III collagens was increased by IL-1 either in the absence or presence of indomethacin. These cells were more responsive to the hIL-1 beta preparation than to the mIL-1 alpha (half-maximal stimulation of PGE2 production was observed at approximately 2.5-5 pM hIL-1 beta and at approximately 2.5 nM mIL-1 alpha). Levels of alpha 1 (I), alpha 2(I), and alpha 1(III) procollagen mRNAs measured by cytoplasmic dot hybridization paralleled the levels of collagens synthesized under the various experimental conditions. IL-1, therefore, is one product of monocytes capable of modulating collagen synthesis by these human mesenchymal cells probably by altering collagen gene expression. These studies suggest that both positive (IL-1) and negative (PGE2) signals may control collagen synthesis at the transcriptional level resulting in modulation of matrix turnover in cartilage, synovium, and skin.