α1-adrenergic receptor antagonists induce production of IL-18 and expression of ICAM-1 and CD40 in human monocytes

Hideo Kohka Takahashi, Hiromi Iwagaki, Ryuji Tamura, Goutarou Katsuno, Dong Xue, Sachi Sugita, Shuji Mori, Tadashi Yoshino, Noriaki Tanaka, Masahiro Nishibori

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Abstract

The activation of T cells plays a role in antitumor response. Monocytes activate T cells by inducing the cell-to-cell interaction that involves the engagement of adhesion molecules with their ligands, and the production of IL-18. The authors examined the effect of the quinazoline-based α1-adrenergic receptor antagonists bunazosin, doxazosin, prazosin, and terazosin on the expression of adhesion molecules such as ICAM-1, B7.1, B7.2, CD40, and CD40L on monocytes isolated from human peripheral blood mononuclear cells. Doxazosin, prazosin, and terazosin induced the expression of ICAM-1 and CD40 but had no effect on the expression of B7.1, B7.2, and CD40L. Moreover, IL-18 was detected in the medium of incubated monocytes treated with doxazosin, prazosin, and terazosin. Bunazosin did not affect adhesion molecule expression and IL-18 production, suggesting that the chemical structure of quinazoline might not be related to the effect of doxazosin, prazosin, and terazosin. Although caspase-1 inhibitor completely abolished the production of IL-18, anti-IL-18 mAb and caspase-1 inhibitor partially inhibited the increase in ICAM-1 and CD40 expression induced by doxazosin, prazosin, and terazosin. Doxazosin, prazosin, and terazosin can induce monocyte activation with a specific pattern of expression of adhesion molecules and IL-18 production, and this may lead to T-cell activation through the cell-to-cell interaction. The activation of T cells induced by the increase of the expression of ICAM-1 and CD40 and the production of IL-18 may be involved in the anti-cancer effects of doxazosin, prazosin, and terazosin.

Original languageEnglish
Pages (from-to)40-43
Number of pages4
JournalJournal of Immunotherapy
Volume28
Issue number1
Publication statusPublished - Jan 2005

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Keywords

  • α1-antagonists
  • CD40
  • ICAM-1
  • IL-18
  • Monocytes

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Takahashi, H. K., Iwagaki, H., Tamura, R., Katsuno, G., Xue, D., Sugita, S., Mori, S., Yoshino, T., Tanaka, N., & Nishibori, M. (2005). α1-adrenergic receptor antagonists induce production of IL-18 and expression of ICAM-1 and CD40 in human monocytes. Journal of Immunotherapy, 28(1), 40-43.