SHORT REPORT
Cotinine inhibits the pro-inflammatory response initiated by multiple cell surface Toll-like receptors in monocytic THP cells
Juhi Bagaitkar 1, 2,   Iris Zeller 3,   Diane E Renaud 3,   David A Scott 1, 3  
 
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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
CORRESPONDING AUTHOR
David A Scott   

Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA
Publication date: 2012-11-23
 
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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