Regulation of cytokine-induced human C-reactive protein production by transforming growth factor-beta.
Transforming growth factor-beta (TGF-beta) modified production of the major human acute phase reactant, C-reactive protein (CRP), induced by the inflammatory cytokines, IL-1 beta or IL-6. CRP mRNA accumulation in the hepatoma PLC/PRF/5 cell line was slightly more rapid, but of smaller magnitude in response to IL-1 beta (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-beta at concentrations greater than or equal to 0.1 pg/ml inhibited the induced IL-1 or IL-6 CRP production; whereas concentrations less than 0.1 pg/ml slightly enhanced CRP synthesis. Addition of TGF-beta 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-beta and IL-6, although CRP protein synthesis was inhibited. A similar pattern of inhibition of CRP production by TGF-beta 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-beta was added to the cells before the cytokine. This enhanced CRP response was sensitive to cycloheximide. TGF-beta 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-beta before IL-6 addition. Therefore, TGF-beta is potentially a potent regulator of CRP synthesis by hepatocytes at the post-transcriptional level.
Taylor
A W
AW
Department of Microbiology, Ohio State University, Columbus 43210-1292.
Ku
N O
NO
Mortensen
R F
RF
D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002097:C-Reactive Protein / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D002097:C-Reactive Protein