Blocking effect of anti-mouse interleukin-6 monoclonal antibody and glucocorticoid receptor antagonist, RU38486, on metallothionein-inducing activity of serum from lipopolysaccharide-treated mice.
Although there is much evidence to suggest that lipopolysaccharide (LPS)-induced elevation of hepatic metallothionein (MT) contents is mediated by cytokines, the presence of MT-inducing activity in the serum of LPS-treated animals has not been examined. It was found that serum from LPS-treated mice stimulated MT induction in a hepatoma cell culture. The MT-inducing activity in serum was highest 2 h after LPS injection. Tumor necrosis factor and interleukin (IL)-6 levels in the serum were highest 1 and 2 h, respectively, after LPS injection. Anti-mouse IL-6 monoclonal antibody neutralized MT-inducing activity in serum obtained from mice 2 h after LPS injection. The MT-inducing activity in serum was blocked by the glucocorticoid antagonist, RU38486. A similar requirement for glucocorticoid was also observed in an IL-6-stimulated culture. These results show that the LPS-induced elevation of hepatic MT is mediated by IL-6, and the expression of the stimulating activity of IL-6 is dependent on the presence of glucocorticoid.
Itoh
N
N
Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Kasutani
K
K
Muto
N
N
Otaki
N
N
Kimura
M
M
Tanaka
K
K
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000931:Antidotes / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002460:Cell Line; D002606:Charcoal / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D005470:Fluorometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006727:Hormone Antagonists / Q000494:pharmacology*; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008113:Liver Neoplasms / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000097:blood* / Q000235:genetics; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology*; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000931:Antidotes; D001798:Blood Proteins; D006727:Hormone Antagonists; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D002606:Charcoal; D015735:Mifepristone; D008668:Metallothionein; D003345:Corticosterone