Effect of cytokines on the secretion of the fifth and eighth complement components by HepG2 cells.
Liver cells can be induced by interleukin-1, tumor necrosis factor and interleukin-6 to secrete higher amounts of complement components. Information, so far available only for the early components, indicates that these cytokines exhibit different effects on various complement proteins. For instance, they promote the biosynthesis of C3 and B but have no effect on that of C4 and C2. These observations led us to evaluate the ability of interleukin-1, tumor necrosis factor and interleukin-6 to modulate the secretion of the late complement components by HepG2 cells, a human hepatoma-derived cell line known to produce several complement proteins. The amount of complement components in the culture supernatant was evaluated by a sensitive enzyme-linked immunosorbent assay revealing picogram levels of these proteins. The HepG2 cells were found to secrete a substantial amount of C3 (approximately 1 microgram/10(6) cells), easily detectable C5 (approximately 150 ng/10(6) cells) and C8 (approximately 10 ng/10(6) cells) and a low amount of C6 (approximately 0.5 ng/10(6) cells), whereas the levels of both C7 and C9 could not be measured. The addition of interleukin-1, tumor necrosis factor and interleukin-6 to the cell culture resulted in an enhanced secretion of C8, whereas that of C5 was only marginally increased. None of these cytokines had a clear effect on the secretion of C6 nor induced the production of C7 and C9.(ABSTRACT TRUNCATED AT 250 WORDS)
Perissutti
S
S
Istituto per l'Infanzia Burlo Garofolo, Università di Trieste, Italy.
Tedesco
F
F
D006528:Carcinoma, Hepatocellular / Q000473:pathology; D003182:Complement C5 / Q000378:metabolism*; D003185:Complement C8 / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D003182:Complement C5; D003185:Complement C8; D007375:Interleukin-1; D015850:Interleukin-6; D009363:Neoplasm Proteins; D014409:Tumor Necrosis Factor-alpha