First Author | Gabay C | Year | 2001 |
Journal | Eur J Immunol | Volume | 31 |
Issue | 2 | Pages | 490-9 |
PubMed ID | 11180114 | Mgi Jnum | J:134201 |
Mgi Id | MGI:3785125 | Doi | 10.1002/1521-4141(200102)31:2<490::aid-immu490>3.0.co;2-h |
Citation | Gabay C, et al. (2001) Production of IL-1 receptor antagonist by hepatocytes is regulated as an acute-phase protein in vivo. Eur J Immunol 31(2):490-9 |
abstractText | 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. |