Activation of the monocytic α7 nicotinic acetylcholine receptor modulates oxidative stress and inflammation-associated development of coronary artery spasm via a p38 MAP-kinase signaling-dependent pathway

Ming-Yow Hung, Yi-Hong Wu, Oluwaseun Adebayo Bamodu, Xi Chen, Yen-Kuang Lin, Patrick Hu, Nen-Chung Chang, Jong-Hwei Su Pang, Chi-Tai Yeh

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: Smoking and high-sensitivity C-reactive protein (hs-CRP) are risk factors for coronary artery spasm (CAS), which is characterized by the increased interleukin-6 (IL-6) level and monocyte counts; however, limited data are available regarding the role of cigarette-embedded nicotine in the modulation of monocytic inflammatory activity in CAS.

APPROACH: We investigated and elucidated the putative roles and associations of nicotine, monocytic IL-6, α7 nicotinic acetylcholine receptor (α7-nAChR), and CRP in CAS development.

RESULTS: We demonstrated that a significantly increased α7-nAChR (p = 0.001) and IL-6 (p = 0.0036) messenger RNA (mRNA) expression in the serum of patients with CAS. Serum hs-CRP levels exhibited a strong positive correlation with the monocytic mRNA expression of α7-nAChR (r = 0.71, p < 0.001) and IL-6 (r = 0.49, p = 0.006). The α7-nAChR and IL-6 expression levels of the CAS group were also positively correlated (r = 0.63, p < 0.001). Compared with the untreated controls, THP-1 cells and patient-derived monocytes treated with different concentrations of CRP displayed significantly increased expression levels of α7-nAChR mRNA and protein (p = 0.0054), in a dose-dependent manner. We also demonstrated that compared with the IL-6 expression elicited by CRP alone (p = 0.0489), the CRP-induced rise in monocytic IL-6 mRNA and protein expression in the presence of nicotine (p = 0.0002), is mediated by α7-nAChR activation and the deregulation of the human p38 mitogen-activated protein kinases (MAPK) signaling pathway.

CONCLUSIONS: Our data demonstrate that the elevated monocytic IL-6 and α7-nAChR mRNA and protein expression levels are associated with the interaction between nicotine and CRP positively modulates CAS development. Our study suggests the potential role of α7-nAChR mRNA and/or protein expression as a diagnostic biomarker for CAS.

LanguageEnglish
Pages266-276
Number of pages11
JournalFree Radical Biology and Medicine
Volume120
DOIs
Publication statusPublished - May 20 2018

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Oxidative stress
MAP Kinase Signaling System
Nicotinic Receptors
Spasm
p38 Mitogen-Activated Protein Kinases
Interleukin-6
Coronary Vessels
Oxidative Stress
Chemical activation
Inflammation
Nicotine
Messenger RNA
C-Reactive Protein
Monocytes
Proteins
Deregulation
Biomarkers
Serum
Tobacco Products
Smoking

Cite this

@article{19c47371f44642f9ba67497d4fb79997,
title = "Activation of the monocytic α7 nicotinic acetylcholine receptor modulates oxidative stress and inflammation-associated development of coronary artery spasm via a p38 MAP-kinase signaling-dependent pathway",
abstract = "OBJECTIVE: Smoking and high-sensitivity C-reactive protein (hs-CRP) are risk factors for coronary artery spasm (CAS), which is characterized by the increased interleukin-6 (IL-6) level and monocyte counts; however, limited data are available regarding the role of cigarette-embedded nicotine in the modulation of monocytic inflammatory activity in CAS.APPROACH: We investigated and elucidated the putative roles and associations of nicotine, monocytic IL-6, α7 nicotinic acetylcholine receptor (α7-nAChR), and CRP in CAS development.RESULTS: We demonstrated that a significantly increased α7-nAChR (p = 0.001) and IL-6 (p = 0.0036) messenger RNA (mRNA) expression in the serum of patients with CAS. Serum hs-CRP levels exhibited a strong positive correlation with the monocytic mRNA expression of α7-nAChR (r = 0.71, p < 0.001) and IL-6 (r = 0.49, p = 0.006). The α7-nAChR and IL-6 expression levels of the CAS group were also positively correlated (r = 0.63, p < 0.001). Compared with the untreated controls, THP-1 cells and patient-derived monocytes treated with different concentrations of CRP displayed significantly increased expression levels of α7-nAChR mRNA and protein (p = 0.0054), in a dose-dependent manner. We also demonstrated that compared with the IL-6 expression elicited by CRP alone (p = 0.0489), the CRP-induced rise in monocytic IL-6 mRNA and protein expression in the presence of nicotine (p = 0.0002), is mediated by α7-nAChR activation and the deregulation of the human p38 mitogen-activated protein kinases (MAPK) signaling pathway.CONCLUSIONS: Our data demonstrate that the elevated monocytic IL-6 and α7-nAChR mRNA and protein expression levels are associated with the interaction between nicotine and CRP positively modulates CAS development. Our study suggests the potential role of α7-nAChR mRNA and/or protein expression as a diagnostic biomarker for CAS.",
author = "Ming-Yow Hung and Yi-Hong Wu and Bamodu, {Oluwaseun Adebayo} and Xi Chen and Yen-Kuang Lin and Patrick Hu and Nen-Chung Chang and Pang, {Jong-Hwei Su} and Chi-Tai Yeh",
note = "Copyright {\circledC} 2018 Elsevier Inc. All rights reserved.",
year = "2018",
month = "5",
day = "20",
doi = "10.1016/j.freeradbiomed.2018.03.050",
language = "English",
volume = "120",
pages = "266--276",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Activation of the monocytic α7 nicotinic acetylcholine receptor modulates oxidative stress and inflammation-associated development of coronary artery spasm via a p38 MAP-kinase signaling-dependent pathway

AU - Hung, Ming-Yow

AU - Wu, Yi-Hong

AU - Bamodu, Oluwaseun Adebayo

AU - Chen, Xi

AU - Lin, Yen-Kuang

AU - Hu, Patrick

AU - Chang, Nen-Chung

AU - Pang, Jong-Hwei Su

AU - Yeh, Chi-Tai

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/5/20

Y1 - 2018/5/20

N2 - OBJECTIVE: Smoking and high-sensitivity C-reactive protein (hs-CRP) are risk factors for coronary artery spasm (CAS), which is characterized by the increased interleukin-6 (IL-6) level and monocyte counts; however, limited data are available regarding the role of cigarette-embedded nicotine in the modulation of monocytic inflammatory activity in CAS.APPROACH: We investigated and elucidated the putative roles and associations of nicotine, monocytic IL-6, α7 nicotinic acetylcholine receptor (α7-nAChR), and CRP in CAS development.RESULTS: We demonstrated that a significantly increased α7-nAChR (p = 0.001) and IL-6 (p = 0.0036) messenger RNA (mRNA) expression in the serum of patients with CAS. Serum hs-CRP levels exhibited a strong positive correlation with the monocytic mRNA expression of α7-nAChR (r = 0.71, p < 0.001) and IL-6 (r = 0.49, p = 0.006). The α7-nAChR and IL-6 expression levels of the CAS group were also positively correlated (r = 0.63, p < 0.001). Compared with the untreated controls, THP-1 cells and patient-derived monocytes treated with different concentrations of CRP displayed significantly increased expression levels of α7-nAChR mRNA and protein (p = 0.0054), in a dose-dependent manner. We also demonstrated that compared with the IL-6 expression elicited by CRP alone (p = 0.0489), the CRP-induced rise in monocytic IL-6 mRNA and protein expression in the presence of nicotine (p = 0.0002), is mediated by α7-nAChR activation and the deregulation of the human p38 mitogen-activated protein kinases (MAPK) signaling pathway.CONCLUSIONS: Our data demonstrate that the elevated monocytic IL-6 and α7-nAChR mRNA and protein expression levels are associated with the interaction between nicotine and CRP positively modulates CAS development. Our study suggests the potential role of α7-nAChR mRNA and/or protein expression as a diagnostic biomarker for CAS.

AB - OBJECTIVE: Smoking and high-sensitivity C-reactive protein (hs-CRP) are risk factors for coronary artery spasm (CAS), which is characterized by the increased interleukin-6 (IL-6) level and monocyte counts; however, limited data are available regarding the role of cigarette-embedded nicotine in the modulation of monocytic inflammatory activity in CAS.APPROACH: We investigated and elucidated the putative roles and associations of nicotine, monocytic IL-6, α7 nicotinic acetylcholine receptor (α7-nAChR), and CRP in CAS development.RESULTS: We demonstrated that a significantly increased α7-nAChR (p = 0.001) and IL-6 (p = 0.0036) messenger RNA (mRNA) expression in the serum of patients with CAS. Serum hs-CRP levels exhibited a strong positive correlation with the monocytic mRNA expression of α7-nAChR (r = 0.71, p < 0.001) and IL-6 (r = 0.49, p = 0.006). The α7-nAChR and IL-6 expression levels of the CAS group were also positively correlated (r = 0.63, p < 0.001). Compared with the untreated controls, THP-1 cells and patient-derived monocytes treated with different concentrations of CRP displayed significantly increased expression levels of α7-nAChR mRNA and protein (p = 0.0054), in a dose-dependent manner. We also demonstrated that compared with the IL-6 expression elicited by CRP alone (p = 0.0489), the CRP-induced rise in monocytic IL-6 mRNA and protein expression in the presence of nicotine (p = 0.0002), is mediated by α7-nAChR activation and the deregulation of the human p38 mitogen-activated protein kinases (MAPK) signaling pathway.CONCLUSIONS: Our data demonstrate that the elevated monocytic IL-6 and α7-nAChR mRNA and protein expression levels are associated with the interaction between nicotine and CRP positively modulates CAS development. Our study suggests the potential role of α7-nAChR mRNA and/or protein expression as a diagnostic biomarker for CAS.

U2 - 10.1016/j.freeradbiomed.2018.03.050

DO - 10.1016/j.freeradbiomed.2018.03.050

M3 - Article

VL - 120

SP - 266

EP - 276

JO - Free Radical Biology and Medicine

T2 - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

ER -