Differential expression and release of cd54 induced by cytokines

Judith K. Mickelson, Gilbert Kukielka, J. Stanley Bravenec, Elizabeth Mainolfi, Robert Rothlein, Hal K. Hawkins, James H. Kelly, C. Wayne Smith

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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-1β (IL-1β), tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), 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-1β (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 IL6, cytokine-induced hepatocyte surface levels of ICAM1 (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 IL-1β and TNFa; 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 cICAM1 levels. In human lung adenocarcinoma cells, the cytokine induction of ICAM-1 mRNA could potentially be accounted for by observing cell surface levels of ICAM1 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.

Original languageEnglish (US)
Pages (from-to)866-875
Number of pages10
Issue number3
StatePublished - Sep 1995
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology


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