Document Type

Article

Publication Date

5-15-1993

Comments

This research was originally published in Journal of Biological Chemistry. Diazr, A., Munoz, E., Johnston, R., Korn, J. H., & Jimenez, S. A.. Regulation of human lung fibroblast alpha 1(I) procollagen gene expression by tumor necrosis factor alpha, interleukin-1 beta, and prostaglandin E2. Journal of Biological Chemistry. 1993; 268(14):10364-10371. © the American Society for Biochemistry and Molecular Biology.

Abstract

We investigated the participation of prostaglandin (PG) E2 in the regulation of the alpha 1(I) procollagen gene expression by tumor necrosis factor alpha (TNF alpha), and interleukin-1 beta (IL-1 beta) in normal adult human lung fibroblasts. TNF alpha (100 units/ml) and IL-1 beta (100 units/ml) stimulated the production of PGE2 and caused a dose-dependent inhibition of up to 54 and 66%, respectively, of the production of type I procollagen. Preincubation of cultures with indomethacin partially reversed the inhibition of procollagen production induced by the cytokines. Cytokine-stimulated endogenous fibroblast PG accounted for 35 and 68% of the inhibition induced by TNF alpha and IL-1 beta, respectively. Steady-state mRNA levels for alpha 1(I) procollagen paralleled the changes in collagen production. The transcription rate of the alpha 1(I) procollagen gene was reduced by 58% by TNF alpha and by 43% by IL-1 beta. Cytokine-stimulated endogenous PG production accounted for half of these effects. These results indicate that TNF alpha and IL-1 beta inhibit the expression of the alpha 1(I) procollagen gene in human lung fibroblasts at the transcriptional level by a PGE2-independent effect as well as through the effect of endogenous fibroblast PGE2 released under the stimulus of the cytokines.

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