Interleukin 1 beta down-regulates collagen and augments collagenase expression in human intestinal smooth muscle cells

Background & Aims: Smooth muscle cells resident in the intestinal wall play a significant role in the healing of the injured intestine and in the fibrosis that complicates Crohn's disease. The cytokine interleukin 1 beta (IL-1 beta) is involved in inflammatory bower disease. The aim of this study was to determine the action of IL-1 beta on proliferation and collagen metabolism in human intestinal smooth muscle cells. Results: IL-beta caused a threefold increase in [H-3]thymidine uptake at 100 pmol/L. This mitogenic effect was equipotent with that of platelet-derived growth factor when cells were exposed to IL-beta for 48 vs. 24 hours. IL-beta inhibited the secretion of procollagen into culture medium by 70% and the accumulation of newly synthesized procollagen in cells by 55%. In addition, IL-beta caused a concentration-dependent inhibition of steady-state levels of procollagen I and III messenger RNA (85% inhibition at 100 pmol/L) and a 3-5 fold augmentation of collagenase messenger RNA levels. Conclusions: IL-beta is mitogenic for human intestinal smooth muscle cells, but this action is associated with a concomitant down-regulation of collagen synthesis and secretion and an augmention of collagenase expression.