Release of interleukin-1 beta by dermatan sulfate suppresses hepatocyte growth

Among glycosaminoglycans, dermatan sulfate (DS) is the strongest inhibitor of DNA synthesis in adult rat hepatocytes in primary culture stimulated with insulin and epidermal growth factor. Hyaluronate also inhibited DNA synthesis, whereas chondroitin-6 sulfate, 4-sulfate or heparin had no effect on DNA synthesis in hepatocytes. Analysis of growth regulatory factors in hepatocyte culture medium treated with DS revealed that interleukin-1 (IL-1) was released into the medium. IL-1 beta mRNA was detected in DS-treated hepatocytes by reverse transcriptase-polymerase chain reaction, but not in untreated hepatocytes. For a marked inhibition of DNA synthesis, more than 10 hr of exposure to DS before cultured hepatocytes started DNA synthesis, was required. Similarly, more than 10 hr was required after the addition of DS before IL-1 beta mRNA was detected. These findings suggest that DS in the medium induced the production of IL-1 beta which, in turn, reduced DNA synthesis in hepatocytes.