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

Fujii, Yoshihito X.; Fujigaya, Hirofumi; Moriwaki, Yuji; Misawa, Hidemi; Kimura, Tadashi; Grando, Sergei A.; Kawashima, Koichiro

doi:10.1016/j.jneuroim.2007.07.003

Cited by 86 publications

(58 citation statements)

References 24 publications

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“…22 We have previously demonstrated that upon immunization with ovalbumin, the a7 nAChR knockout mice develop increased serum level of antigen-specific IgG 1 . 23 In marked contrast, immunized M 1 /M 5 mAChR knockout mice show diminished antigen-specific IgG 1 production. 24 The reported pro-inflammatory/immunostimulatory effects of nicotine include increased secretion of IL-12 by Th1 T cells, 25 enhanced Con A-induced production of IFN-g 26 and protection of lymphocytes from cortisol-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

et al. 2011

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Acetylcholine (ACh) regulates vital functions of T cells by acting on the nicotinic and muscarinic classes of cholinergic receptors, nAChR and mAChRs, respectively. This study was performed in murine splenic T cells. In freshly isolated CD4 and CD8 T cells, we detected mRNAs encoding a5, a9, a10, b1, b2, b4 nAChR subunits and M 1 , M 3 , M 4 and M 5 mAChR subtypes, whereas a2 was detected only in CD8 T cells. In vitro activation of CD4 T cells through T-cell receptor (TCR)/CD3 cross-linking was associated with the appearance of a4 and a7, upregulation of a5, a10, b4, M 1 and M 5 and downregulation of a9 and b2, whereas in vitro activation of CD8 T cells also featured the appearance of a4 and a7, as well as upregulation of a2, a5, b4, M 1 and M 4 , and downregulation of a10, b1, b2 and M 3 . In vitro polarization toward T helper (Th) 1 lineage was associated with a decrease of b2, b4 and M 3 expression; that toward Th2 cells with downregulation of a9 and M 3 , and upregulation of M 1 and M 5 ; and that toward Th17 phenotype with downregulation of a9, a10, b2 and M 3 mAChR. Polarized T cells also expressed a4, but not a1, a2, a3, a6, b3 or M 2 . To determine the role of cholinergic receptors in mediating the immunoregulatory action of autocrine/paracrine ACh, we analyzed the effects of nicotinic and muscarinic agonists ± antagonists on cytokine production in the CD4 þ CD62L þ T cells co-stimulated via TCR/CD3 cross-linking. The nicotinergic stimulation upregulated interferon-g (IFN-g) and downregulated interleukin (IL)-17 secretion, whereas the muscarinic stimulation enhanced IL-10 and IL-17 and inhibited INF-g secretion. These results demonstrated plasticity of the T-cell cholinergic system.

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Section: Discussionmentioning

confidence: 99%

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

et al. 2011

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“…The ␣7 nAChR is also now known as an essential regulator of inflammation. 21,70 Its inactivation or down-expression may contribute to the excessive proinflammatory pathway, the increased fragility of the airway epithelium and the altered epithelium regeneration observed in COPD. Most patients with COPD have a history of chronic smoking.…”

Section: Discussionmentioning

confidence: 99%

α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

Maouche

Polette

Jolly

et al. 2009

The American Journal of Pathology

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Airway epithelial basal cells are known to be critical for regenerating injured epithelium and maintaining tissue homeostasis. Recent evidence suggests that the ␣7 nicotinic acetylcholine receptor (nAChR), which is highly permeable to Ca 2؉ , is involved in lung morphogenesis. Here, we have investigated the potential role of the ␣7 nAChR in the regulation of airway epithelial basal cell proliferation and the differentiation of the human airway epithelium. In vivo during fetal development and in vitro during the regeneration of the human airway epithelium, ␣7 nAChR expression coincides with epithelium differentiation. Inactivating ␣7 nAChR function in vitro increases cell proliferation during the initial steps of the epithelium regeneration, leading to epithelial alterations such as basal cell hyperplasia and squamous metaplasia, remodeling observed in many bronchopulmonary diseases. The regeneration of the airway epithelium after injury in ␣7 The respiratory epithelium, which is constantly exposed to airborne pollutants, is frequently injured, which results in altered epithelial functions. To restore these functions, the respiratory epithelium must undergo rapid repair via epithelial cell spreading and migration and regenerate its structure via basal cell proliferation and differentiation.

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“…Also, immune suppression may reduce surveillance for abnormal cells, a condition that would favor the growth of transformed cells and possibly cancer. In contrast to the effects of nicotine on the immune response (suppressive), others (Fujii et al, 2007) report that immunization of nAChRα7KO mice results in enhanced production of antigen-specific IgG(1) suggesting that this nicotinic receptor plays a role in cytokine production affecting immunoglobulin synthesis. Further investigations selecting different mouse strains of appropriate genetic susceptibility or experimental design, to define the importance of different nAChRs to this process, the route of inflammatory stimulation and how this system contributes to these processes appears to be of potential clinical relevance and extends the function of the neuronal nicotinic receptors to regulating important components of inflammatory and immune function.…”

Section: Discussionmentioning

confidence: 99%

“…However, nAChRs are also expressed by non-neuronal cells throughout the body where they contribute to diverse physiological processes including immunomodulation (Fujii et al, 2007). Mature nAChRs are pentamers of subunit assemblages from 11 genetically related but distinct subunits (Hogg et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation

Osborne-Hereford

Rogers

Gahring

2008

Journal of Neuroimmunology

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The anti-inflammatory effects of the neuronal nicotinic receptor alpha7 (nAChRα7) are proposed to require acetylcholine release from vagal efferents. The necessity for vagal innervation in this antiinflammatory pathway was tested in the skin, which lacks parasympathetic innervation, using ultraviolet radiation (UVB) to induce a local pro-inflammatory response. Cytokine responses to UV in mice administered chronic oral nicotine, a nAChR agonist, were reduced. Conversely, nAChRα7 knock-out mice exposed to UVB elicit an enhanced pro-inflammatory cytokine response in the skin. Altered pro-inflammatory responses correlated with changes in SOCS3 protein. These results demonstrate that nAChRα7 can participate in modulating a local pro-inflammatory response in the absence of parasympathetic innervation.

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

Cited by 86 publications

References 24 publications

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

Plasticity of the murine spleen T-cell cholinergic receptors and their role in in vitro differentiation of naïve CD4 T cells toward the Th1, Th2 and Th17 lineages

α7 Nicotinic Acetylcholine Receptor Regulates Airway Epithelium Differentiation by Controlling Basal Cell Proliferation

Neuronal nicotinic alpha7 receptors modulate inflammatory cytokine production in the skin following ultraviolet radiation

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