α7 Nicotinic Acetylcholine Receptor Stimulation Inhibits Lipopolysaccharide-Induced Interleukin-18 and -12 Production in Monocytes

Abstract

Abstract. Nicotine inhibited interleukin (IL)-18 and -12 production in lipopolysaccharide (LPS)-stimulated monocytes, and the action of nicotine was antagonized by a non-selective and a selective α7 nicotinic acetylcholine receptor (α7-nAChR) antagonist, suggesting that the stimulation of α7-nAChR may be involved in the action of nicotine. Nicotine is reported to induce prostaglandin E 2 (PGE 2 ) production in monocytes through the up-regulation of cyclooxygenase (COX)-2 expression. PGE 2 is known to increase cAMP levels and to activate protein kinase A (PKA). COX-2 and PKA inhibitors prevented the action of nicotine, indicating that the mechanism of action of nicotine may be via endogenous PGE 2 production.

Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic responses in inflammatory bowel disease?

“…32 Other studies have shown that nicotine decreases IL1␤, TNF␣, and TGF␤ production. 22,24 -26,60 The ␣-7 nicotinic acetyl choline receptor (␣7-nAChR), through which nicotine has its effect, is expressed on peripheral blood monocytes and lymphocytes 61,62 ; in this study both cell types were affected by nicotine, with perhaps a stronger effect on monocyte-derived cytokines, especially in response to LPS, as there was no effect on the specific T-cell cytokine IL2. Conversely, for the cell cycle, nicotine had no effect on LPS-stimulated responses, but increased resting cells and reducing S-phase proliferation in response to PHA, concurring with previous studies demonstrating that nicotine induced G 0 /G 1 cell cycle arrest in T cells.…”

Nicotine and inflammatory neurological disorders

“…Pretreatment with low-dose nicotine causes inhibition of the production of IL-12, IFN-γ, prostaglandin E2, macrophage inflammatory protein (MIP)-1 and TNF-α. In addition, nicotine suppresses the phosphorylation of I-κB thereby inhibiting the transcriptional activity of NF-κB and suppressing HMGB1 release [31,[49][50][51] . These suppressive effects of nicotine occur at the transcriptional level and are mediated through α7nAChR.…”

Haplotypic analysis of tag SNPs of the interleukin-18 gene in relation to cardiovascular disease events: the MORGAM Project

“…The consistency of this finding across the five cohorts reduces the likelihood that this is a chance finding. However, even if nicotine has been found to be associated with IL-18 levels 24,25 and interactions between smoking and inflammatory gene SNPs have already been observed in the context of atherosclerosis, 26 genetic results of this significance do not often replicate, given the small prior that an individual SNP, no matter how good a candidate gene it resides in, has to show a gene -smoking interaction effect on CVD. Further work in large sample studies are therefore required to confirm the result observed in this report.…”