TY - JOUR
T1 - Essential role of ICAM-1/LFA-1 interaction in synergistic effect of IL-18 and IL-12 on IFN-γ production in human PBMC
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
N1 - Funding Information:
Acknowledgements The authors thank Ms. Miyuki Shiotani for her excellent technical assistance. This study was supported in part by a grant from the Japan Society for Promotion of Science (BSAR-521/0003815). The experiments comply with the current laws of Japan. We obtained an oral informed consent from voluntary blood donors.
PY - 2002
Y1 - 2002
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.
KW - ICAM-1
KW - IFN-γ
KW - IL-12
KW - IL-18
KW - LFA-1
KW - Monocytes
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U2 - 10.1007/s00210-001-0518-6
DO - 10.1007/s00210-001-0518-6
M3 - Article
C2 - 11882913
AN - SCOPUS:0036193180
SN - 0028-1298
VL - 365
SP - 181
EP - 186
JO - Naunyn-Schmiedeberg's Archives of Pharmacology
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
IS - 3
ER -