Dexamethasone increases PECAM–1-gene-expression but decreases ICAM–1 expression in rat liver and in mononuclear phagocytes

Aims: Previously we demonstrated that PECAM–1 is expressed in mononuclear cells (MNP) and sinusoidal endothelial cells (SEC) of the rat liver. PECAM–1-gege-expression is down-regulated in the course of an acute CCl₄ induced liver injury as well as in vitro in SEC and in MNP after treatment with INF-γ or TNF-α while ICAM–1 I up-regulated. Corticosteroids are known to down-regulate ICAM–1 expression. Methods and results: In this study we show, that in livers from rats treated with CCl4 and dexamethasone (DEX) the onset of necrosis as well as the recovery was retarded compared to the sole treatment with CCl₄. Northern blot analysis indicated that there was no increase of ICAM–1 specific transcripts 3h to 12h but there was a retarded increase in ICAM–1 specific transcripts 48h following the combined treatment with DEX and CCl₄. In contrast there was an early increase of PECAM–1 specific transcripts detectable in livers from rats treated with DEX and CCl_4. Treatment of cultured small or large MNP with dexamethasone increased the transcript level of PECAM–1 dose dependently, whereas in parallel the ICAM–1 transcript level was decreased. Since recently we had identified IFN-γ as a potential effector of PECAM–1 down-regulation following CCl₄ treatment, we measured IFN-γ levels in DEX+CCl₄ treated livers, indicating a lack of the increase of IFN-γ protein level in contrast to solely CCl₄ treated animals. Conclusions: Following DEX treatment in vivo and in vitro, PECAM–1 expression is increased, whereas ICAM–1 expression is decreased. The missing increase in IFN-γ might be responsible for the increase of PECAM–1 following DEX and CCl₄ administration.

PECAM-1; ICAM-1; Liver; mononuclear phagocytes; corticosteroids