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

33 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

Fingerprint

Interleukin-18
Nicotine
Monocytes
Cytokines
Cyclooxygenase 2
Cyclic AMP-Dependent Protein Kinases
Mecamylamine
Bungarotoxins
Nicotinic Receptors
Intercellular Adhesion Molecule-1
Interleukin-12
Protein Kinase Inhibitors
Cell Communication
Cyclic AMP
Anti-Inflammatory Agents
Up-Regulation
Macrophages
T-Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology

Cite this

Effect of nicotine on IL-18-initiated immune response in human monocytes. / Takahashi, Hideo Kohka; Iwagaki, Hiromi; Hamano, Ryosuke; Yoshino, Tadashi; Tanaka, Noriaki; Nishibori, Masahiro.

In: Journal of Leukocyte Biology, Vol. 80, No. 6, 12.2006, p. 1388-1394.

Research output: Contribution to journalArticle

Takahashi, Hideo Kohka ; Iwagaki, Hiromi ; Hamano, Ryosuke ; Yoshino, Tadashi ; Tanaka, Noriaki ; Nishibori, Masahiro. / Effect of nicotine on IL-18-initiated immune response in human monocytes. In: Journal of Leukocyte Biology. 2006 ; Vol. 80, No. 6. pp. 1388-1394.
@article{a43d8b8d62544c629867d3b871b97e6b,
title = "Effect of nicotine on IL-18-initiated immune response in human monocytes",
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.",
keywords = "B7, CD40, ICAM-1, Nicotine acetylcholine receptor α7 subunit, Prostaglandin E2",
author = "Takahashi, {Hideo Kohka} and Hiromi Iwagaki and Ryosuke Hamano and Tadashi Yoshino and Noriaki Tanaka and Masahiro Nishibori",
year = "2006",
month = "12",
doi = "10.1189/jlb.0406236",
language = "English",
volume = "80",
pages = "1388--1394",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "6",

}

TY - JOUR

T1 - Effect of nicotine on IL-18-initiated immune response in human monocytes

AU - Takahashi, Hideo Kohka

AU - Iwagaki, Hiromi

AU - Hamano, Ryosuke

AU - Yoshino, Tadashi

AU - Tanaka, Noriaki

AU - Nishibori, Masahiro

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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.

KW - B7

KW - CD40

KW - ICAM-1

KW - Nicotine acetylcholine receptor α7 subunit

KW - Prostaglandin E2

UR - http://www.scopus.com/inward/record.url?scp=33845405542&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845405542&partnerID=8YFLogxK

U2 - 10.1189/jlb.0406236

DO - 10.1189/jlb.0406236

M3 - Article

VL - 80

SP - 1388

EP - 1394

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 6

ER -