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pubmed-article:8079364pubmed:abstractTextWe have previously reported that the hormone-supplemented culture condition for primary hepatocytes is required in dimethylnitrosamine (DMN)-induced suppression of antibody response to sheep erythrocytes in the mixed cultures of murine hepatocytes and splenocytes. In the present investigation, the components of the hormone supplement were screened to identify the component(s) responsible for the increased ability of hepatocytes to activate DMN to its immunosuppressive form. The presence of hydrocortisone in the hepatocyte culture media had the primary role in DMN activation in the co-culture system. Other components of the hormone supplement showed slight or no effects. The effects of hydrocortisone were clearly confirmed through the dose-response study of both DMN and hydrocortisone. To characterize whether the effect of hydrocortisone is glucocorticoid-dependent we tested another potent glucocorticoid, dexamethasone (DEX), and determined if the activity by hydrocortisone could be reversed by RU 486. It was found that hepatocytes cultured in DEX-containing media could also activate DMN to its immunosuppressive form. However, the activity by hydrocortisone to increase DMN-induced immunosuppression was not reversed by RU 486. Furthermore, a possible direct interaction between DMN and hydrocortisone was ruled out. Finally, we transferred DMN-pre-treated culture supernatant from hepatocytes to spleen cell cultures, and found that the metabolite of DMN was very unstable, and that DMN-induced suppression of T-dependent antibody response was hepatocyte-dependent. The present results suggest that glucocorticoids, including hydrocortisone and DEX, in hepatocyte culture media can affect DMN-induced immunosuppression in the hepatocyte/splenocyte co-culture system via a pathway which does not appear to be related to the glucocorticoid receptor.lld:pubmed
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pubmed-article:8079364pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:8079364pubmed:articleTitleRole of hydrocortisone in dimethylnitrosamine-induced suppression of antibody response in the mixed culture of murine hepatocytes and splenocytes.lld:pubmed
pubmed-article:8079364pubmed:affiliationDepartment of Pharmacology and Toxicology, Medical College of Virginia/Virginia Commonwealth University, Richmond.lld:pubmed
pubmed-article:8079364pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:8079364pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed