SHORT REPORT
Cotinine inhibits the pro-inflammatory response initiated by multiple cell surface Toll-like receptors in monocytic THP cells
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1
Microbiology and Immunology, University of Louisville, Louisville, USA
 
2
Currently: Department of Pediatrics, Washington University School of Medicine, St. Louis, USA
 
3
Oral Health and Systemic Disease Research Group, University of Louisville, Louisville, USA
 
 
Submission date: 2012-10-18
 
 
Acceptance date: 2012-11-21
 
 
Publication date: 2012-11-23
 
 
Corresponding author
David A Scott   

Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA
 
 
Tobacco Induced Diseases 2012;10(November):18
 
KEYWORDS
ABSTRACT
Background:
The primary, stable metabolite of nicotine [(S)-3-(1-methyl-2-pyrrolidinyl) pyridine] in humans is cotinine [(S)-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone]. We have previously shown that cotinine exposure induces convergence and amplification of the GSK3β-dependent PI3 kinase and cholinergic anti-inflammatory systems. The consequence is reduced pro-inflammatory cytokine secretion by human monocytes responding to bacteria or LPS, a TLR4 agonist.

Findings:
Here we show that cotinine-induced inflammatory suppression may not be restricted to individual Toll-like receptors (TLRs). Indeed, in monocytic cells, cotinine suppresses the cytokine production that is normally resultant upon agonist-specific engagement of all of the major surface exposed TLRs (TLR 2/1; 2/6; 4 and 5), although the degree of suppression varies by TLR.

Conclusions:
These results provide further mechanistic insight into the increased susceptibility to multiple bacterial infections known to occur in smokers. They also establish THP-1 cells as a potentially suitable model with which to study the influence of tobacco components and metabolites on TLR-initiated inflammatory events.

 
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CITATIONS (13):
1.
GSK3β and the control of infectious bacterial diseases
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Trends in Microbiology
 
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Carcinogenesis
 
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2-Amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine is an anti-inflammatory TLR-2, -4 and -5 response mediator in human monocytes
Huizhi Wang, Mark W. Graves, Huaxin Zhou, Zhen Gu, Richard J. Lamont, David A. Scott
Inflammation Research
 
4.
Positive modulators of the α7 nicotinic receptor against neuroinflammation and cognitive impairment in Alzheimer's disease
Valentina Echeverria, Alex Yarkov, Gjumrakch Aliev
Progress in Neurobiology
 
5.
Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice
J. Alex Grizzell, Alexandre Iarkov, Rosalee Holmes, Takahashi Mori, Valentina Echeverria
Behavioural Brain Research
 
6.
Interferon-γ-induced inflammatory markers and the risk of cancer: The Hordaland Health Study
Hui Zuo, Grethe S. Tell, Stein E. Vollset, Per M. Ueland, Ottar Nygård, Øivind Midttun, Klaus Meyer, Arve Ulvik, Simone J.P.M. Eussen
Cancer
 
7.
Tobacco-induced suppression of the vascular response to dental plaque
N. Buduneli, D.A. Scott
Molecular Oral Microbiology
 
8.
Enhanced Anti-inflammatory Activity of Peptide–Gold Nanoparticle Hybrids upon Cigarette Smoke Extract Modification through TLR Inhibition and Autophagy Induction
Wei Gao, Lu Wang, Kun Wang, Liya Sun, Yafei Rao, Aying Ma, Min Zhang, Qiang Li, Hong Yang
ACS Applied Materials & Interfaces
 
9.
Marijuana-Derived Cannabinoids Trigger a CB2/PI3K Axis of Suppression of the Innate Response to Oral Pathogens
Zhen Gu, Shilpa Singh, Rajarshi Niyogi, Gwyneth Lamont, Huizhi Wang, Richard Lamont, David Scott
Frontiers in Immunology
 
10.
Cotinine and 6-Hydroxy-L-Nicotine Reverses Memory Deficits and Reduces Oxidative Stress in Aβ25-35-Induced Rat Model of Alzheimer’s Disease
Razvan Boiangiu, Marius Mihasan, Dragos Gorgan, Bogdan Stache, Brindusa Petre, Lucian Hritcu
Antioxidants
 
11.
The inflammatory biomarker YKL-40 is elevated in the serum, but not the sputum, of E-cigarette users
Mario Perez, Nkiruka Atuegwu, Eric Mortensen, Cheryl Oncken
Experimental Lung Research
 
12.
Nicotinic acetylcholine receptors and learning and memory deficits in Neuroinflammatory diseases
Valentina Echeverria, Cristhian Mendoza, Alex Iarkov
Frontiers in Neuroscience
 
13.
Nicotine improves DSS-induced colitis by inhibiting NLRP3 and altering gut microbiota
Yi-Xiang Zhang, Xiao-Qian Chi, Meng Li, Wei Zhang, Ying Guan, Lian-Qiu Wu
Journal of Asian Natural Products Research
 
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