Regulation of cytokine-induced human C-reactive protein production by transforming growth factor-β1

A. W. Taylor, N. O. Ku, R. F. Mortensen

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Abstract

Transforming growth factor-β (TGF-β) modified production of the major human acute phase reactant, C-reactive protein (CRP), induced by the inflammatory cytokines, IL-1β or IL-6. CRP mRNA accumulation in the hepatoma PLC/PRF/5 cell line was slightly more rapid, but of a smaller magnitude in response to IL-1β (fourfold increase) than to IL-6 (10-fold increase); however, the amount of CRP protein accumulating in the culture medium was similar for both cytokines. TGF-β at concentrations ≥0.1 pg/ml inhibited the induced IL-1 or IL-6 CRP production; whereas concentrations ≥0.1 pg/ml slightly enhanced CRP synthesis. Addition of TGF-β to the cultures up to 16 h after the PLC/PRF/5 cells were already exposed to IL-1 or IL-6 resulted in the cessation of CRP production. CRP mRNA accumulated in hepatoma cells treated with both TGF-β and IL-6, although CRP protein synthesis was inhibited. A similar pattern of inhibition of CRP production by TGF-β occurred when Hep 3B.2 cells were treated with a mixture of IL-1 and IL-6. Enhanced production of CRP was observed only when TGF-β was added to the cells before the cytokine. This enhanced CRP response was sensitive to cycloheximide. TGF-β added along with IL-6 inhibited the metabolic labeling of CRP with [35S]methionine; however, enhanced incorporation of [35S]methionine into CRP was observed when the cells were exposed to TGF-β before IL-6 addition. Therefore, TGF-β is potentially a potent regulator of CRP synthesis by hepatocytes at the post-transcriptional level.

Original languageEnglish
Pages (from-to)2507-2513
Number of pages7
JournalJournal of Immunology
Volume145
Issue number8
Publication statusPublished - 1990 Jan 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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