Interleukin 1β and phorbol ester induce tumour necrosis factor α production in a hepatic cell line (HepG2)

Tumour necrosis factor α (TNFα) is a pleiotropic cytokine that is produced mainly by monocytes and macrophages. TNFα appears to be responsible for many of the inflammatory and necrotic changes seen in malignant or infectious liver diseases. In addition, blood levels of TNFα have been reported to be elevated in those with hepatic diseases. Although TNFα is synthesized mainly by monocytes and macrophages, its production has recently been found in nonhaemopoietic cells as well. Therefore we have used the human liver cell line HepG2 to test for the inducible production of TNFα in hepatic parenchymal cells. No constitutive TNFα gene expression was detected by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). However, treatment with the proinflammatory cytokine interleukin 1β (IL-1β) or phorbol 12-myristate-acetate (PMA) led to a marked increase in TNFα mRNA levels. Maximal TNFα mRNA levels were observed after 3-h incubation periods, decreased thereafter and became undetectable after 12 h. The culture supernatant from cells treated with IL-1β or PMA contained significant amounts of TNFα protein which was immunologically detectable and biologically active. We believe that our report of inducible TNFα production in this widely available hepatic cell line adds a valuable tool for understanding TNFα gene expression in nonhaematopoietic cells.