Essential role of ICAM-1/LFA-1 interaction in synergistic effect of IL-18 and IL-12 on IFN-γ production in human PBMC

Atsushi Yoshida, Hideo Kohka Takahashi, Hiromi Iwagaki, Tadashi Yoshino, Toshihiko Morichika, Minori Yokoyama, Hideyuki Itoh, Shuji Mori, Tadaatsu Akagi, Masahiro Nishibori, Noriaki Tanaka

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

IL-18 (0-100 ng/ml) specifically upregulated ICAM-1 expression on monocytes in human PBMC as demonstrated in our previous study. In the present study, we examined whether the synergistic upregulation of ICAM-1 occurred after the stimulation with the combination of IL-18 and IL-12 and whether the synergistic production of IFN-γ was dependent on the interaction between ICAM-1 on monocytes and LFA-1 on NK/T cells. The effect of IL-12 on ICAM-1 expression on monocytes was marginal even at the highest concentration (100 ng/ml). However, in the presence of IL-12 (100 ng/ml), the expression of ICAM-1 induced by IL-18 was significantly enhanced as compared with that obtained by IL-18 alone. In addition to the expression of ICAM-1 on monocytes, IFN-γ production was synergistically stimulated by IL-18 and IL-12. Anti-ICAM-1 and anti-LFA-1 Abs exhibited significant inhibitory effect on enhanced production of IFN-γ by the combination of two cytokines, in particular, anti-ICAM-1 showing the complete inhibition. These results as a whole indicated that synergistic effect of IL-18 and IL-12 on IFN-γ production in human PBMC is ascribed to the synergism of the effect of two cytokines on ICAM-1 expression on monocytes and that the subsequent ICAM-1/LFA-1 interaction plays an important role in the enhanced production of IFN-γ.

Original languageEnglish
Pages (from-to)181-186
Number of pages6
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume365
Issue number3
DOIs
Publication statusPublished - 2002

Fingerprint

Lymphocyte Function-Associated Antigen-1
Interleukin-18
Intercellular Adhesion Molecule-1
Interleukin-12
Monocytes
Cytokines
Natural Killer Cells
Up-Regulation
T-Lymphocytes

Keywords

  • ICAM-1
  • IFN-γ
  • IL-12
  • IL-18
  • LFA-1
  • Monocytes

ASJC Scopus subject areas

  • Pharmacology

Cite this

Essential role of ICAM-1/LFA-1 interaction in synergistic effect of IL-18 and IL-12 on IFN-γ production in human PBMC. / Yoshida, Atsushi; Takahashi, Hideo Kohka; Iwagaki, Hiromi; Yoshino, Tadashi; Morichika, Toshihiko; Yokoyama, Minori; Itoh, Hideyuki; Mori, Shuji; Akagi, Tadaatsu; Nishibori, Masahiro; Tanaka, Noriaki.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 365, No. 3, 2002, p. 181-186.

Research output: Contribution to journalArticle

Yoshida, Atsushi ; Takahashi, Hideo Kohka ; Iwagaki, Hiromi ; Yoshino, Tadashi ; Morichika, Toshihiko ; Yokoyama, Minori ; Itoh, Hideyuki ; Mori, Shuji ; Akagi, Tadaatsu ; Nishibori, Masahiro ; Tanaka, Noriaki. / Essential role of ICAM-1/LFA-1 interaction in synergistic effect of IL-18 and IL-12 on IFN-γ production in human PBMC. In: Naunyn-Schmiedeberg's Archives of Pharmacology. 2002 ; Vol. 365, No. 3. pp. 181-186.
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AU - Yoshida, Atsushi

AU - Takahashi, Hideo Kohka

AU - Iwagaki, Hiromi

AU - Yoshino, Tadashi

AU - Morichika, Toshihiko

AU - Yokoyama, Minori

AU - Itoh, Hideyuki

AU - Mori, Shuji

AU - Akagi, Tadaatsu

AU - Nishibori, Masahiro

AU - Tanaka, Noriaki

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N2 - IL-18 (0-100 ng/ml) specifically upregulated ICAM-1 expression on monocytes in human PBMC as demonstrated in our previous study. In the present study, we examined whether the synergistic upregulation of ICAM-1 occurred after the stimulation with the combination of IL-18 and IL-12 and whether the synergistic production of IFN-γ was dependent on the interaction between ICAM-1 on monocytes and LFA-1 on NK/T cells. The effect of IL-12 on ICAM-1 expression on monocytes was marginal even at the highest concentration (100 ng/ml). However, in the presence of IL-12 (100 ng/ml), the expression of ICAM-1 induced by IL-18 was significantly enhanced as compared with that obtained by IL-18 alone. In addition to the expression of ICAM-1 on monocytes, IFN-γ production was synergistically stimulated by IL-18 and IL-12. Anti-ICAM-1 and anti-LFA-1 Abs exhibited significant inhibitory effect on enhanced production of IFN-γ by the combination of two cytokines, in particular, anti-ICAM-1 showing the complete inhibition. These results as a whole indicated that synergistic effect of IL-18 and IL-12 on IFN-γ production in human PBMC is ascribed to the synergism of the effect of two cytokines on ICAM-1 expression on monocytes and that the subsequent ICAM-1/LFA-1 interaction plays an important role in the enhanced production of IFN-γ.

AB - IL-18 (0-100 ng/ml) specifically upregulated ICAM-1 expression on monocytes in human PBMC as demonstrated in our previous study. In the present study, we examined whether the synergistic upregulation of ICAM-1 occurred after the stimulation with the combination of IL-18 and IL-12 and whether the synergistic production of IFN-γ was dependent on the interaction between ICAM-1 on monocytes and LFA-1 on NK/T cells. The effect of IL-12 on ICAM-1 expression on monocytes was marginal even at the highest concentration (100 ng/ml). However, in the presence of IL-12 (100 ng/ml), the expression of ICAM-1 induced by IL-18 was significantly enhanced as compared with that obtained by IL-18 alone. In addition to the expression of ICAM-1 on monocytes, IFN-γ production was synergistically stimulated by IL-18 and IL-12. Anti-ICAM-1 and anti-LFA-1 Abs exhibited significant inhibitory effect on enhanced production of IFN-γ by the combination of two cytokines, in particular, anti-ICAM-1 showing the complete inhibition. These results as a whole indicated that synergistic effect of IL-18 and IL-12 on IFN-γ production in human PBMC is ascribed to the synergism of the effect of two cytokines on ICAM-1 expression on monocytes and that the subsequent ICAM-1/LFA-1 interaction plays an important role in the enhanced production of IFN-γ.

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