Comparative effects of interleukin-1 and tumor necrosis factor-α on collagen production and corresponding procollagen mrna levels in human dermal fibroblasts

Abstract

The effects of recombinant human Interleukin-1α (IL-1α), Interleukin-1β (IL-1β), and Tumor Necrosis Factor-α (TNF-α) on collagen biosynthesis were studied in vitro using dermal fibroblast cultures. Both forms of IL-1 and TNF-α induced a dose-dependent inhibition of both types I and III collagen synthesis, as measured by radioimmunoassay, gel electrophoresis, or collagenase-sensitive material. This effect was accompanied by a significant release of postaglandin E2 into the culture medium. However, indomethacin, a potent inhibitor of prostaglandin synthesis, could not prevent the inhibitory effect of the three cytokines on collagen synthesis. Measurement of type I and type III procollagen mRNA levels in IL-1 treated cells revealed that both IL-1α and IL-1β were potent enhancers of procollagen gene expression at pretranslational level. On the other hand, TNF-α was found to reduce the steady-state levels of type I and III procollagen mRNA in a dose-dependent manner. Quantitation of IL-1β and TNF-α transcripts following TNF-α treatment of fibroblasts indicated that this cytokine can induce IL-1β gene expression in these cells. By contrast, TNF-α mRNA remained at a constant level after TNF-α exposure. These data suggest that IL-1 and TNF-α, two cytokines that share several biologic activities, modulate collagen deposition in dermal fibroblasts by mechanisms that are clearly different: TNF-α appears to act at a transcriptional level to inhibit collagen synthesis, whereas IL-1 inhibitory action involves important translational regulation, still unknown, that counterbalances its stimulatory effect on procollagen mRNA levels. Moreover, our data suggest the existence of local fibroblastic cytokine production that may be involved in the modulation of extracellular matrix deposition. © 1991.