Differential regulation of interleukin-6 expression in human fibroblasts by tumor necrosis factor-α and lymphotoxin

• Published in: FEBS letters 1990-09, Vol.270 (1), p.152-156
• Main Authors: Mantovani, Luisa, Henschler, Reinhard, Brach, Marion A., Wieser, Raimund, Lübbert, Michael, Lindemann, Albrecht, Mertelsmann, Roland H., Herrmann, Friedhelm
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Cells, Cultured; Fibroblasts - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Humans; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Kinetics; Lymphotoxin-alpha - physiology; Molecular and cellular biology; Molecular genetics; Protein Biosynthesis; Protein Kinase C - physiology; RNA, Messenger - metabolism; Time Factors; Transcription, Genetic; Tumor Necrosis Factor-alpha - physiology
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(90)81256-N

The treatment of human diploid fibroblasts with tumor necrosis factor (TNP)-α and with lymphotoxin (LT) is associated with induction of interleuk-in-6 (IL-6) transcripts with TNF-α being 10-fold more potent than LT. Here we report on the TNF-α/LT-induced signaling mechanisms responsible for the regulation of IL-6 gene expression in these cells. Run-on assays demonstrated that both TNF-α and LT increase IL-6 mRNA levels by transcriptional activation of this gene. Stability studies of IL-6 transcripts in fibroblasts showed that TNF-α delayed IL-6 mRNA decay but not LT. The induction of IL-6 transcripts by TNF-α and LT was not inhibited by the isoquinoline sulfonamide derivative H7. Similarly, depletion of protein kinase C (PKC) by 12- O-tetradecanoyl-phorbol 13-acetate (TPA) did not change the ability of TNF-α and LT to induce IL-6 transcripts, demonstrating that stimulation by these agents may not be mediated by activation of PKC. Stimulation of IL-6 transcripts in fibroblasts did also not require new protein synthesis as exposure to the protein synthesis inhibitor cycloheximide (CHX) enhanced accumulation of IL-6 mRNA in the presence or absence of TNF-α or LT.