Abstract
Interleukin-1β (IL-1β) is a potent signal for the induction of the matrix-degrading enzymes collagenase and stromelysin. These metalloproteinases (MMP) play a critical role in physiologic and pathologic connective tissue remodeling, and are potential targets for therapeutic manipulation. Treatment of human dermal fibroblasts with interferon-γ inhibited Type I collagen gene expression, and abrogated the effect of IL-1β on MMP expression. Interferon-γ also caused a dramatic dose-dependent increase in indoleamine 2,3-dioxygenase mRNA, with consequent depletion of tryptophan and accumulation of kynurenine in the culture media. To examine the role of tryptophan metabolism in the effects of interferon-γ on matrix-degrading enzymes, exogenous tryptophan was added to tryptophan-depleted media, followed by stimulation of the cultures with IL-1β. Supplementation with tryptophan completely overcame the inhibitory effects of interferon-γ on MMP mRNA expression and metalloproteinase secretion into the media. In contrast, mRNA levels for Type I collagen remained profoundly depressed in interferon-γ-treated cultures in spite of addition of exogenous tryptophan. These results indicate that oxidative tryptophan metabolism mediates the effects of interferon-γ on MMP gene expression in human fibroblasts.
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© 1996 Plenum Press, New York
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Varga, J., Yufit, T., Hitraya, E., Brown, R.R. (1996). Control of Extracellular Matrix Degradation by Interferon-γ. In: Filippini, G.A., Costa, C.V.L., Bertazzo, A. (eds) Recent Advances in Tryptophan Research. Advances in Experimental Medicine and Biology, vol 398. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0381-7_23
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DOI: https://doi.org/10.1007/978-1-4613-0381-7_23
Publisher Name: Springer, Boston, MA
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