Nicotine-mediated signals modulate cell death and survival of T lymphocytes

Oloris, Sı́lvia Catarina Salgado; Frazer‐Abel, Ashley; Jubala, Cristan M.; Fosmire, Susan; Helm, Karen M.; Robinson, Sally R.; Korpela, Derek M.; Duckett, Megan M.; Baksh, Shairaz; Modiano, Jaime F.

doi:10.1016/j.taap.2009.10.020

Cited by 26 publications

(22 citation statements)

References 60 publications

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“…Our data are consistent with previous studies showing that α7-nAChR-like radioligand binding sites are present in total lymphocyte populations (De Rosa et al, 2009, De Rosa et al, 2005, Sato et al, 1999, Yoshikawa et al, 2006), immortalized T cell lines (Oloris et al, 2009, Razani-Boroujerdi et al, 2007) and primary cultures of CD4 + T cells (Nizri et al, 2009). Our finding that nAChR α7 subunit message levels in T cells increase after MOG immunization suggests that levels of receptor-like binding sites also might increase in response to such a challenge and perhaps upon growth in primary cell culture or after immortalization (Oloris et al, 2009).…”

Section: Discussionsupporting

confidence: 93%

“…Our finding that nAChR α7 subunit message levels in T cells increase after MOG immunization suggests that levels of receptor-like binding sites also might increase in response to such a challenge and perhaps upon growth in primary cell culture or after immortalization (Oloris et al, 2009). Further work is needed to define the dynamics of nAChR expression in immune cells, as their mediation of nicotinic effects also could vary depending on conditions and models used.…”

Section: Discussionmentioning

confidence: 99%

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Attenuation of CNS inflammatory responses by nicotine involves α7 and non-α7 nicotinic receptors

Hao¹,

Simard²,

Turner³

et al. 2011

Experimental Neurology

107

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A considerable number of in vivo studies have demonstrated that the cholinergic system can dampen the peripheral immune response, and it is thought that the α7-nicotinic acetylcholine receptor (nAChR) subtype is a key mediator of this process. The goal of the present study was to determine if nicotine modulates immunological mechanisms known to be involved in the development of experimental autoimmune encephalomyelitis (EAE), a mouse model for CNS autoimmune disease, via α7-nAChRs. Here we show that nicotine exposure attenuates EAE severity and that this effect is largely abolished in nAChR α7 subunit knock-out mice. However, nicotine exposure partially retains the ability to reduce lymphocyte infiltration into the CNS, inhibit auto-reactive T cell proliferation and helper T cell cytokine production, down-regulate costimulatory protein expression on myeloid cells, and increase the differentiation and recruitment of regulatory T cells, even in the absence of α7-nAChRs. Diverse effects of nicotine on effector and regulatory T cells, as well as antigen presenting cells, may be linked to differential expression patterns of nAChR subunits across these cell types. Taken together, our data show that although α7-nAChRs indeed seem to play an important role in nicotine-conferred reduction of the CNS inflammatory response and protection against EAE, other nAChR subtypes also are involved in the anti-inflammatory properties of the cholinergic system.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Attenuation of CNS inflammatory responses by nicotine involves α7 and non-α7 nicotinic receptors

Hao¹,

Simard²,

Turner³

et al. 2011

Experimental Neurology

107

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“…However, disparate and sometimes conflicting reports as to the mechanisms of nicotinic cholinergic mediation of anti-inflammatory effects need to be reconciled before a complete understanding can be achieved. For example, exposure to nicotine has been reported to activate the nuclear factor of activated T cells transcription factor in lymphocytes and endothelial cells, resulting in alterations in cell growth and vascular endothelial growth factor production [153]. Additional studies suggest that nicotine stimulates COX-2 expression via the activation of NF- κ B and subsequent release of proinflammatory mediators, such as prostaglandin E2 (PGE2), IL-1 β , IL-6, nitric oxide, and TNF- α in human gingival fibroblasts [154, 155].…”

Section: Future Directionsmentioning

confidence: 99%

“…Furthermore, anti-inflammatory effects mediated by alpha7 nicotinic receptors can be synergistic with other signaling systems such as steroids and are mediated through reduction of nuclear translocation of p65 to suppress cytokine expression [156]. Nicotine has also been shown to have paradoxical effects that might alternatively enforce survival or trigger apoptosis, suggesting that depending on timing and context, nicotine might act either as a survival factor or as an inducer of apoptosis in normal or transformed lymphocytes, and possibly other nonneuronal cells [153]. Similar paradoxical effects have been reported for other targets involved in inflammation.…”

Section: Future Directionsmentioning

confidence: 99%

Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases

Bencherif¹,

Lippiello²,

Lucas

et al. 2010

Cell. Mol. Life Sci.

185

143

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In recent years the etiopathology of a number of debilitating diseases such as type 2 diabetes, arthritis, atherosclerosis, psoriasis, asthma, cystic fibrosis, sepsis, and ulcerative colitis has increasingly been linked to runaway cytokine-mediated inflammation. Cytokine-based therapeutic agents play a major role in the treatment of these diseases. However, the temporospatial changes in various cytokines are still poorly understood and attempts to date have focused on the inhibition of specific cytokines such as TNF-α. As an alternative approach, a number of preclinical studies have confirmed the therapeutic potential of targeting alpha7 nicotinic acetylcholine receptor-mediated anti-inflammatory effects through modulation of proinflammatory cytokines. This “cholinergic anti-inflammatory pathway” modulates the immune system through cholinergic mechanisms that act on alpha7 receptors expressed on macrophages and immune cells. If the preclinical findings translate into human efficacy this approach could potentially provide new therapies for treating a broad array of intractable diseases and conditions with inflammatory components.

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“…The effects of nicotine on cell proliferation, apoptosis and angiogenesis are mediated by nicotine’s interaction with the nAChR (6,7) and genome wide association study studies have implicated a gene locus (15q25) that encodes three nAChR subunits in lung cancer risk (14–16). Some investigators have suggested this association is a direct link to lung cancer, independent from any effect on nicotine addiction and smoking intensity (7,17).…”

Section: Introductionmentioning

confidence: 99%

Chronic Nicotine Consumption Does Not Influence 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis

Murphy¹,

Schutten²,

Kassie³

et al. 2011

Cancer Prevention Research

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Nicotine replacement therapy (NRT) is often used to maintain smoking cessation. However, concerns exist about the safety of long term NRT use in ex-smokers and its concurrent use in smokers. In this study, we determined the effect of nicotine administration on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumors in A/J mice. Female mice were administered a single dose of NNK (10 μmol) and 0.44 μmol/ml nicotine in the drinking water. Nicotine was administered 2 weeks prior to NNK, 44 weeks after NNK, throughout the experiment, or without NNK treatment. The average weekly consumption of nicotine-containing water was 15 ± 3 mls/mouse, resulting in an estimated daily nicotine dose of 0.9 μmol (0.15 mg) per mouse. Nicotine administration alone for 46 weeks did not increase lung tumor multiplicity (0.32 ± 0.1 tumor/mouse versus 0.53 ± 0.1 tumors/mouse). Lung tumor multiplicity in NNK-treated mice was 18.4 ± 4.5 and was not different than for mice consuming nicotine before or after NNK administration, 21.9 ± 5.3 and 20.0 ± 5.4 tumors per mouse, respectively. Lung tumor multiplicity in animals consuming nicotine both before and after NNK administration was 20.4 ± 5.4. Tumor size and progression of adenomas to carcinomas was also not affected by nicotine consumption. In addition, nicotine consumption had no effect on the level of O6-methylguanine in the lung of NNK-treated mice. These negative findings in a commonly used model of human lung carcinogenesis should lead us to question the interpretation of the many in vitro studies that find nicotine stimulates cancer cell growth.

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Nicotine-mediated signals modulate cell death and survival of T lymphocytes

Cited by 26 publications

References 60 publications

Attenuation of CNS inflammatory responses by nicotine involves α7 and non-α7 nicotinic receptors

Attenuation of CNS inflammatory responses by nicotine involves α7 and non-α7 nicotinic receptors

Alpha7 nicotinic receptors as novel therapeutic targets for inflammation-based diseases

Chronic Nicotine Consumption Does Not Influence 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone–Induced Lung Tumorigenesis

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