Effect of nicotine on IL-18-initiated immune response in human monocytes

Hideo Kohka Takahashi, Hiromi Iwagaki, Ryosuke Hamano, Tadashi Yoshino, Noriaki Tanaka, Masahiro Nishibori

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Nicotine is thought to inhibit the production of proinflammatory cytokines from macrophages through an anti-inflammatory pathway that is dependent on nicotinic acetylcholine receptor α7 subunit (α7-nAChR). IL-18, an important proinflammatory cytokine, is reported to induce the expression of adhesion molecules on monocytes, thus enhancing cell-to-cell interactions with T-cells and contributing to IL-18-initiated cytokine production. Accordingly, inhibition of IL-18 suppresses systemic inflammatory responses. In the present study, we found that nicotine inhibited the IL-18-enhanced expression of ICAM-1, B7.2, and CD40 on monocytes, and the production of IL-12, IFN-γ, and TNF-α by PBMC. A nonselective and a selective α7-nAChR antagonist, mecamylamine, and α-bungarotoxin abolished the effects of nicotine, suggesting that this depends on α7-nAChR stimulation. It is reported that nicotine induces prostaglandinE2 (PGE2) production in PBMC through the up-regulation of cyclooxygenase (COX)-2 expression. PGE2 is known to activate the EP2/EP4-receptor, leading to an increase in cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity. Consistent with this, we found that COX-2 and PKA inhibitors prevented the effects of nicotine on adhesion molecule expression and cytokine production, indicating that the mechanism of action of nicotine may be via endogenous PGE2 production.

Original languageEnglish
Pages (from-to)1388-1394
Number of pages7
JournalJournal of Leukocyte Biology
Volume80
Issue number6
DOIs
Publication statusPublished - Dec 2006

Keywords

  • B7
  • CD40
  • ICAM-1
  • Nicotine acetylcholine receptor α7 subunit
  • Prostaglandin E2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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