Production of IL-1 receptor antagonist by hepatocytes is regulated as an acute-phase protein in vivo.
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| Abstract |
IL-1 receptor antagonist (IL-1Ra) is produced by isolated human hepatocytes with characteristics of an acute-phase protein. There are multiple IL-1Ra peptides, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, 2, 3). sIL-1Ra, but not icIL-1Ra1, mRNA is transcribed by cultured human hepatocytes. In this study, we examined in vivo production of IL-1Ra by the liver in mice in two experimental models of acute-phase response, systemic lipopolysaccharide (LPS) administration and local turpentine injection. Liver sIL-1Ra expression was up-regulated in response to both types of stimulation. After LPS injection, the hepatic production of sIL-1Ra correlated with the increase in plasma IL-1Ra levels. In addition, the total amount of IL-1Ra present in the liver after LPS injection was six- and tenfold higher than in the lung and spleen. As assessed by in situ hybridization, sIL-1Ra, but not icIL-1Ra, mRNA was produced by hepatocytes in vivo after LPS injection. Using IL-6(-/-) mice, we demonstrated that in turpentine-induced inflammation production of IL-1Ra mRNA by the liver is regulated by IL-6. In contrast, local production of IL-1Ra is independent of IL-6. Taken together, these results indicate that IL-1Ra is produced by the liver as an acute-phase protein in vivo.
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| Authors | C Gabay, J Gigley, J Sipe, W P Arend, G Fantuzzi |
| Journal | European journal of immunology (Eur J Immunol) Vol. 31 Issue 2 Pg. 490-9 (Feb 2001) ISSN: 0014-2980 [Print] Germany |
| PMID | 11180114 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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