Stimulation of α7 nicotinic acetylcholine receptor inhibits CD14 and the toll-like receptor 4 expression in human monocytes

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

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

The lipopolysaccharide (LPS)-receptor complex, CD14/toll-like receptor 4, is known to play a role in the immune responses during sepsis. Excessive inflammation and tumor necrosis factor (TNF)-α synthesis have been reported to cause morbidity and mortality in endotoxemia and sepsis. Cell-to-cell interaction through the engagement between intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and their ligands on T cells has been suggested to play a role in the inflammatory response such as TNF-α and interleukin 10 production. Nicotine, with the stimulation of the nicotinic acetylcholine receptor α7 subunit (α7-nAChR), has now become the focus of attention because of its anti-inflammatory effects. However, little is known about the mechanism of the inhibitory effects induced by nicotine on the LPS-induced immune responses. In the present study, we found that nicotine suppressed the expression of CD14, toll-like receptor 4, intercellular adhesion molecule 1, B7.1, and CD40 on monocytes and the production of TNF-α, but not interleukin 10, in human peripheral blood mononuclear cells in the presence of LPS. The actions of nicotine were reversed by a nonselective and a selective α7-nAChR antagonist, mecamylamine and α-bungarotoxin, respectively. Therefore, nicotine might inhibit the LPS receptor complex expression via α7-nAChR, thus leading to a decrease in the adhesion molecule expression and TNF-α production. Moreover, we demonstrated that a nuclear factor-κB and a p38 mitogen-activated protein kinase inhibitor mimicked the actions of nicotine in the presence of LPS. These results suggested that the nuclear factor-κB and p38 mitogen-activated protein kinase might be involved in the actions of nicotine.

Original languageEnglish
Pages (from-to)358-364
Number of pages7
JournalShock
Volume26
Issue number4
DOIs
Publication statusPublished - Oct 2006

Keywords

  • CD14
  • Lipopolysaccharide
  • Monocyte
  • Nicotine
  • Nicotinic acetylcholine receptor α7 subunit
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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