Selective regulation of intercellular adhesion molecule-1 expression by interleukin-18 and interleukin-12 on human monocytes

Abstract

Induction of expression of adhesion molecules is a crucial step in inflammation. The role of interleukin-18 (IL-18) in induction of various adhesion molecules was investigated in freshly isolated peripheral blood mononuclear cells and human monocyte and T-cell lines. IL-18 selectively up-regulated intercellular adhesion molecule-1 (ICAM-1) expression on freshly isolated human monocytes, but not on lymphocytes. The expression of other adhesion molecules was not influenced. Induction of ICAM-1 by IL-18 was dependent on endogenous tumour necrosis factor-alpha (TNF-alpha), and IL-12 had an additive effect on that of IL-18. No changes in adhesion molecule expression were observed on the monocytic cell line THP-1 and on the T-cell lines HSB-2 and Jurkat J16. In addition, induction of ICAM-1 on monocytes by lipopolysaccharide was slightly, but significantly, inhibited by blockade of either endogenous IL-18 or TNF-alpha with IL-18 binding protein or TNF binding protein, respectively. Blocking IL-1 effects with IL-1 receptor antagonist did not influence ICAM-1 levels. In conclusion, IL-18 selectively up-regulates the expression of ICAM-1 on monocytes, and this contributes to the proinflammatory effects of this cytokine.

Figure 1

Effect of IL-18 on ICAM-1 expression on freshly isolated PBMC. PBMC were stimulated with or without IL-18 (1 µg/ml), and ICAM-1 expression on monocytes (a) and lymphocytes (b) was assessed after 24 hr of incubation. Data are representative of four similar experiments.

Figure 2

Time-response of IL-18 on ICAM-1 expression. PBMC were stimulated with (open squares) or without (closed squares) IL-18 (1 µg/ml), and ICAM-1 expression on monocytes was assessed after 4, 8, 24, and 48 hr of incubation. Data represent the mean ± SEM of three donors, expressed as mean fluorescence of ICAM-1.

Figure 3

Induction of ICAM-1 by IL-18 and IL-12. PBMC were stimulated with IL-18 (1 µg/ml) and/or IL-12 (10 ng/ml). ICAM-1 expression was assessed after 24 hr of incubation. Data represent the mean ± SEM of nine donors, expressed as mean fluorescence of ICAM-1. *P < 0·01 versus control. **P < 0·05 versus either cytokine alone.

Figure 4

Induction of ICAM-1 by IL-18 and IL-12 is TNF-dependent. (a) PBMC were stimulated with IL-18 (1 µg/ml) or IL-12 (10 ng/ml). TNF-α was measured after 24 hr of incubation. Data represent the mean ± SEM of nine donors. **P < 0·01 versus control. *P < 0·05 versus control. (b) PBMC were stimulated with IL-18 (1 µg/ml) or IL-12 (10 ng/ml) in the absence or presence of TNFbp (10 µg/ml). ICAM-1 expression was assessed after 24 hr of incubation. Data represent the mean ± SEM of five donors, expressed as mean fluorescence of ICAM-1. *P < 0·05.

Figure 5

Role of endogenous IL-18, TNF, and IL-1 in LPS-induced ICAM-1 production. PBMC were stimulated with LPS (1 µg/ml) in the absence or presence of IL-18bp (500 ng/ml), TNFbp (10 µg/ml) or IL-1Ra (10 µg/ml). ICAM-1 expression was assessed after 24 hr of incubation. Data represent the mean ± SEM of six donors, expressed as mean fluorescence of ICAM-1. *P < 0·05 versus LPS.