Microarray analysis of nicotine-induced changes in gene expression in a macrophage-like human cell line.
OBJECTIVE
Cigarette smoking has been suggested as a risk factor for periodontitis. Thousands of components are present in cigarette smoke, including nicotine, which may play an important role in the observed effects of smoking on cell metabolism. However, the mechanisms underlying these effects are unclear. Using DNA microarrays, we monitored differentially expressed genes, responsive to nicotine, in a macrophage-like human cell line.


METHODS
Human U937 cells were treated for 1 h, with or without 1.0 microg/ml of nicotine. For differentiation, cultures were incubated with 10 nm phorbol myristate acetate for 48 h. Analysis of gene expression was performed using a DNA microarray of 8500 genes.


RESULTS
The expression of 4914 genes was detected. Screening was carried out on those genes whose expression in three separate experiments showed an average change of twofold or greater, and 118 up-regulated genes and 97 down-regulated genes were identified. Among these were genes related to inflammation and other immune responses, such as phospholipase A2 and interferon. Consistent with the array findings, we found similar changes in mRNA expression after analysis using the real-time polymerase chain reaction.


CONCLUSIONS
The results suggest that nicotine causes excess inflammation and disturbs host defense mechanisms against pathogens.
Koshi
R
R
Nihon University Graduate School of Dentistry, Tokyo, Japan.
Sugano
N
N
Orii
H
H
Fukuda
T
T
Ito
K
K
D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D054467:Phospholipases A2 / Q000096:biosynthesis; D020298:U937 Cells; D014945:Wound Healing / Q000187:drug effects
D018836:Inflammation Mediators; D018722:Nicotinic Agonists; D009538:Nicotine; D054467:Phospholipases A2