Nicotine stimulated bone marrow-derived dendritic cells could augment HBV specific CTL priming by activating PI3K-Akt pathway

Jin, Hui; Li, Hai Tao; Sui, Hua; Xue, Mao Qiang; Wang, Yi Nan; Wang, Jia Xun; Gao, Feng

doi:10.1016/j.imlet.2012.02.015

Cited by 27 publications

(40 citation statements)

References 45 publications

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“…Multiple factors could possibly contribute to nicotine's positive effects on EAE/MS, since nAChRs are found expressed on different cell populations, including neurons, microglia/macrophages [9], T cells [41], dendritic cells [10], and even oligodendrocyte progenitors [42] and endothelial cells [43]. Type 1 T helper cells (Th1) and Type 17 T helper cells (Th17) are the main pathogenic cells of EAE.…”

Section: Discussionmentioning

confidence: 99%

“…Nicotinic acetylcholine receptors (nAChRs) are expressed by immune cells that play critical roles in MS, including T cells [8], macrophages/microglia [9] and dendritic cells [10], raising the possibility that nicotine might stimulate immunomodulatory pathways that initiate or accelerate MS progression. However, recent studies suggested that nicotine did not promote more severe symptoms during EAE -, but rather inhibited disease development [11].…”

Section: Introductionmentioning

confidence: 99%

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The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components

Gao

Nissen

et al. 2014

PLoS ONE

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Epidemiological studies have reported that cigarette smoking increases the risk of developing multiple sclerosis (MS) and accelerates its progression. However, the molecular mechanisms underlying these effects remain unsettled. We have investigated here the effects of the nicotine and the non-nicotine components in cigarette smoke on MS using the experimental autoimmune encephalomyelitis (EAE) model, and have explored their underlying mechanism of action. Our results show that nicotine ameliorates the severity of EAE, as shown by reduced demyelination, increased body weight, and attenuated microglial activation. Nicotine administration after the development of EAE symptoms prevented further disease exacerbation, suggesting that it might be useful as an EAE/MS therapeutic. In contrast, the remaining components of cigarette smoke, delivered as cigarette smoke condensate (CSC), accelerated and increased adverse clinical symptoms during the early stages of EAE, and we identify a particular cigarette smoke compound, acrolein, as one of the potential mediators. We also show that the mechanisms underlying the opposing effects of nicotine and CSC on EAE are likely due to distinct effects on microglial viability, activation, and function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components

Gao

Nissen

et al. 2014

PLoS ONE

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“…The analyses of human PBMC-derived DCs also found nicotine increased MR expression via PI3K-Akt pathway (Supplementary Figure S3). As nicotine augmented α7 nAChR expression in murine [9] and human DCs (Supplementary Figure S4), the inhibition of α7 nAChR abolished nicotine's effect on MR expression (Supplementary Figure S4) indicates that α7 nAChR increase MR expression via α7 nAChR-PI3K-mTOR-p70S6 pathway.…”

Section: Resultsmentioning

confidence: 99%

Increased translocation of antigens to endosomes and TLR4 mediated endosomal recruitment of TAP contribute to nicotine augmented cross-presentation

Wang

et al. 2016

Oncotarget

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Cross-presentation by dendritic cells (DCs) requires surface molecules such as lectin, CD40, langerin, heat shock protein, mannose receptor, mediated endocytosis, the endosomal translocation of internalized antigen, and the relocation of transporter associated with antigen processing (TAP). Although the activation of α7 nicotinic acetylcholine receptor (α7 nAchR) up-regulate surface molecule expression, augment endocytosis, and enhance cross-presentation, the molecular mechanism of α7 nAchR activation-increased cross-presentation is still poorly understood. In this study, we investigated the role of mannose receptor in nicotine-increased cross-presentation and the mechanism that endotoxins orchestrating the recruitment of TAP toward endosomes. We demonstrated that nicotine increase the expressiones of mannose receptor and Toll-like receptor 4 (TLR4) via PI3K-Akt-mTOR-p70S6 pathway. Both endosomal translocation of mannose receptor-internalized antigens and TLR4 sig- naling are necessary for nicotine-augmented cross-presentation and cross-priming. Importantly, the recruitment of TAP toward endosomes via TLR4-MyD88-IRAK4 signaling contributes to nicotine-increased cross-presentation and cross-activation of T cells. Thus, these data suggest that increased recruitment of TAP to Ag-containing vesicles contributes to the superior cross-presentation efficacy of α7 nAchR activated DCs.

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“…Western blot analysis. Proteins were obtained in lysis buffer as previously described (13). Proteins were loaded onto SDS-PAGE gels for electrophoresis and transferred onto PVDF membranes.…”

Section: Methodsmentioning

confidence: 99%

“…Mitogen-activated protein kinase (MAPK) signaling pathways, which included Erk, SAPK/JNK and p38, play important roles in growth, differentiation, development and cell survival (10)(11)(12). Nicotine has been reported to activate the MAPK pathway in various tissues and cell types (13,14). Other studies have also shown that the inhibition of MAPK pathways is involved in the anti-apoptotic effects and mediates neuroprotection (15).…”

Section: Introductionmentioning

confidence: 99%

Nicotine exerts neuroprotective effects against β-amyloid-induced neurotoxicity in SH-SY5Y cells through the Erk1/2-p38-JNK-dependent signaling pathway

Xue

Liu

Zhang

et al. 2014

International Journal of Molecular Medicine

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Epidemiological data have indicated that smoking tobacco can decrease the risk of developing Alzheimer's disease (AD). Nicotine, a main component of tobacco, has been shown to have therapeutic effects in AD. The aim of the present study was to assess the neuroprotective effects of nicotine against toxicity induced by β-amyloid (Aβ) in relation to cell apoptosis, and to elucidate the role of the activation of the Erk1/2-p38-JNK pathway and the modulation of anti-apoptotic proteins in the nicotine-induced neuroprotective effects. We performed in vitro and in vivo experiments using SH-SY5Y cells and C57BL/6 mice, respectively. The effects of nicotine on cell apoptosis were determined by flow cytmetry and microscopic observation. The effects of nicotine on the expression of anti-apoptotic proteins were also determined by western blot analysis. Our results demonstrated that nicotine protected the SH-SY5Y cells against Aβ25-35-induced toxicity by inhibiting apoptosis and upregulating the expression of anti-apoptotic proteins. As shown by our in vivo experiments, nicotine effectively ameliorated the impairment in spatial working memory induced by Aβ25-35; this was confirmed by a Morris water maze navigation test and further supported by the upregulation of Bcl-2 in the hippocampus of Aβ25-35-injected mice treated with nicotine. The phosphorylation of Erk1/2, p38 and JNK increased following treatment with nicotine in the SH-SY5Y cells, whereas caspase-3 activation was inhibited by treatment with nicotine prior to exposure to Aβ25-35. Of note, these effects of nicotine against Aβ25-35-induced damage were abolished by inhibitors of Erk1/2, p38 and JNK phosphorylation. These ﬁndings suggest that nicotine prevents Aβ25-35-induced neurotoxicity through the inhibition of neuronal apoptosis, and may thus prove to be a potential preventive or therapeutic agent for AD.

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Nicotine stimulated bone marrow-derived dendritic cells could augment HBV specific CTL priming by activating PI3K-Akt pathway

Cited by 27 publications

References 45 publications

The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components

The Experimental Autoimmune Encephalomyelitis Disease Course Is Modulated by Nicotine and Other Cigarette Smoke Components

Increased translocation of antigens to endosomes and TLR4 mediated endosomal recruitment of TAP contribute to nicotine augmented cross-presentation

Nicotine exerts neuroprotective effects against β-amyloid-induced neurotoxicity in SH-SY5Y cells through the Erk1/2-p38-JNK-dependent signaling pathway

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