Acute-phase protein synthesis in human hepatoma cells: differential regulation of serum amyloid A (SAA) and haptoglobin by interleukin-1 and interleukin-6.
Interleukin-6 (IL-6, BSF-2 or IFN-beta 2) is thought to be the major regulator of the acute-phase protein response that follows tissue injury and inflammation, with interleukin-1 (IL-1), tumour necrosis factor and more recently, LIF or HSF III, slightly stimulatory on only certain acute phase proteins. The synthesis of the major acute-phase protein SAA, originally described as being synthesized in response to IL-1, has been claimed recently to be mainly under IL-6 regulation. Our results show that in the human hepatoma cell line HuH-7, IL-1 is the major stimulating cytokine increasing SAA synthesis by a factor in excess of 100-fold. We also show that under most conditions interleukin-6 and tumour necrosis factor stimulate additively in combination with IL-1. Isoelectric focusing has demonstrated that SAA1 and SAA2 alpha are expressed but not SAA2 beta. The HuH-7 cell line is IL-6 responsive since haptoglobin is stimulated mainly by IL-6.
Raynes
J G
JG
Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, England.
Eagling
S
S
McAdam
K P
KP
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular; D004797:Enzyme-Linked Immunosorbent Assay; D006242:Haptoglobins / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D000685:Serum Amyloid A Protein / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D006242:Haptoglobins; D007375:Interleukin-1; D015850:Interleukin-6; D000685:Serum Amyloid A Protein