Differential expression and release of CD54 induced by cytokines

Intercellular adhesion molecule-1 (ICAM-1, CD54) is upregulated in many cell types stimulated by cytokines. A human hepatoblastoma cell line (C3A, a subclone of HepG2/C3 that is currently being used as a surrogate liver) and human lung adenocarcinoma cells (A549) were stimulated with interleukin-β (IL-β), tumor necrosis factor-α (TNFα), interferon-γ (EFNγ), or IL-6 to determine any differences in cell type responsiveness to individual cytokines for ICAM-1 upregulation. Time courses were performed with each cytokine evaluating ICAM-1 mRNA, surface expression, and cICAM-1 in the cell culture media. Between 3 and 6 hours, IL-β (30 U/mL) stimulated the greatest increase in hepatocyte ICAM-1 mRNA, followed by IFNγ (100 U/mL), TNFα (30 U/mL), and IL-6 (100 U/mL) in order of potency. Except for EL-6, cytokine-induced hepatocyte surface levels of ICAM-1 (immunofluorescence flow cytometry, mAb R6.5) were dose dependent, with inhibition at higher concentration. Highest levels followed stimulation with IFNγ (P < .05). Significantly less was found after both EL-1β and TNFα; none was detected after IL-6 (P < .05). In contrast, IL-1β stimulated significantly more cICAM-1 release from hepatocytes than the other cytokines (P < .001), and IL-6 stimulated modest cICAM-1. Between 3 and 6 hours in the A549 cells, IL-1β stimulated the greatest increase in ICAM-1 mRNA, followed by TNFα. Both responses were greater than that observed in the hepatocytes. IFNγ-and IL-6-induced ICAM-1 mRNA synthesis was not different from unstimulated A549 cells. Cytokine-induced A549 surface levels of ICAM-1 (immunofluorescence flow cytometry, mAb R6.5) was highest for IL-1β (peak levels similar to hepatocyte response), modest with TNFα (peak levels less than hepatocytes), detectable with IFNγ (much less than hepatocytes), and nondetectable after IL-6. No cICAM-1 release from A549 cells was induced under any condition. In hepatocytes the amount of ICAM-1 mRNA was best accounted for by considering both cell surface levels of ICAM-1 and cICAM-1 levels. In human lung adenocarcinoma cells, the cytokine induction of ICAM-1 mRNA could potentially be accounted for by observing cell surface levels of ICAM-1 because no cICAM-1 was produced. These results suggest that surface ICAM-1 and cICAM-1 may be differentially controlled by each cytokine and by each parenchymal cell type. (Hepatology 1995; 22:866–875.)