Enhanced serum antigen-specific IgG1 and proinflammatory cytokine production in nicotinic acetylcholine receptor α7 subunit gene knockout mice

Yoshihito X. Fujii, Hirofumi Fujigaya, Yasuhiro Moriwaki, Hidemi Misawa, Tadashi Kasahara, Sergei A. Grando, Koichiro Kawashima

Research output: Contribution to journalArticle

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Abstract

Human and murine immune cells such as mononuclear leukocytes consisting of mainly T and B cells, bone marrow derived dendritic cells (DCs) and macrophages all express various nicotinic acetylcholine (ACh) receptor (nAChR) subunits. Activated T cells and DCs have the ability to synthesize ACh by choline acetyltransferase, suggesting the role of non-neuronal cholinergic system expressed in immune cells in the regulation of immune cell function. Stimulation of human leukemic T and B cell lines with nicotine causes a transient Ca2+-signaling that is antagonized by α-bungarotoxin, suggesting the involvement of α7 subunit. Furthermore, α7 nAChRs have been shown to negatively regulate synthesis and release of tumor necrosis factor (TNF)-α in macrophages. These findings suggest that immune cell function is regulated by its own non-neuronal cholinergic system, at least in part, via α7 nAChR-mediated pathways. In the present study, we tested the role of α7 nAChRs in the regulation of immune function by measuring total serum and antigen-specific IgG1 and IgM, and production of TNF-α, gamma interferon (IFN-γ) and interleukin (IL)-6 in activated spleen cells of nAChR α7 subunit gene knockout (α7 KO) and wild-type C57BL/6J mice immunized with ovalbumin (OVA). We found that serum levels of total and anti-OVA-specific IgG1 were significantly elevated in α7 KO mice, though there were no significant differences in serum levels of total and anti-OVA-specific IgM between the two genotypes. Production of TNF-α, IFN-γ and IL-6 in spleen cells was significantly facilitated in α7 KO mice. Expression of AChE mRNA was not different between the two genotypes. These results suggest that α7 nAChRs are involved in the regulation of cytokine production, through which modulates TNF-α, IFN-γ and IL-6 productions, leading to modification of antibody production, but are not involved in expression of cholinergic components in immune cells.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
JournalJournal of Neuroimmunology
Volume189
Issue number1-2
DOIs
Publication statusPublished - 2007 Sep

Fingerprint

Gene Knockout Techniques
Nicotinic Receptors
Knockout Mice
Immunoglobulin G
Cytokines
Antigens
Serum
Ovalbumin
Tumor Necrosis Factor-alpha
Interleukin-6
T-Lymphocytes
Dendritic Cells
Immunoglobulin M
B-Lymphocytes
Spleen
Macrophages
Genotype
Mononuclear Leukocytes
Bungarotoxins
Choline O-Acetyltransferase

Keywords

  • α7 subunit
  • Acetylcholine
  • IFN-γ
  • IgG
  • IL-6
  • TNF-α

ASJC Scopus subject areas

  • Immunology
  • Clinical Neurology
  • Immunology and Allergy
  • Neurology

Cite this

Enhanced serum antigen-specific IgG1 and proinflammatory cytokine production in nicotinic acetylcholine receptor α7 subunit gene knockout mice. / Fujii, Yoshihito X.; Fujigaya, Hirofumi; Moriwaki, Yasuhiro; Misawa, Hidemi; Kasahara, Tadashi; Grando, Sergei A.; Kawashima, Koichiro.

In: Journal of Neuroimmunology, Vol. 189, No. 1-2, 09.2007, p. 69-74.

Research output: Contribution to journalArticle

Fujii, Yoshihito X. ; Fujigaya, Hirofumi ; Moriwaki, Yasuhiro ; Misawa, Hidemi ; Kasahara, Tadashi ; Grando, Sergei A. ; Kawashima, Koichiro. / Enhanced serum antigen-specific IgG1 and proinflammatory cytokine production in nicotinic acetylcholine receptor α7 subunit gene knockout mice. In: Journal of Neuroimmunology. 2007 ; Vol. 189, No. 1-2. pp. 69-74.
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