| First Author | Hayashi S | Year | 2014 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 307 |
| Issue | 10 | Pages | G968-78 |
| PubMed ID | 25258409 | Mgi Jnum | J:227830 |
| Mgi Id | MGI:5702850 | Doi | 10.1152/ajpgi.00346.2013 |
| Citation | Hayashi S, et al. (2014) Nicotine suppresses acute colitis and colonic tumorigenesis associated with chronic colitis in mice. Am J Physiol Gastrointest Liver Physiol 307(10):G968-78 |
| abstractText | Ulcerative colitis is a chronic inflammatory disease that frequently progresses to colon cancer. The tumor-promoting effect of inflammation is now widely recognized and understood. Recent studies have revealed that treatment with nicotine ameliorates colitis in humans and experimental murine models, whereas the effect of nicotine on colitis-associated colonic tumorigenesis remains unclear. In the present study, we examined the effect of nicotine on the development of acute colitis and colitis-associated cancer (CAC). The acute colitis model was induced by treatment with 3% dextran sulfate sodium (DSS) for 7 days, whereas the CAC model was induced by a combination of azoxymethane and repeated DSS treatment. Nicotine and a selective agonist of the alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) reduced the severity of DSS-induced acute colonic inflammation. In addition, the suppressive effect of nicotine on acute colitis was attenuated by an antagonist of alpha7-nAChR. Furthermore, nicotine inhibited the IL-6 production of CD4 T cells in the DSS-induced inflamed colonic mucosa. We found that nicotine significantly reduced the number and size of colonic tumors in mice with CAC. Nicotine markedly inhibited the elevation of TNF-alpha and IL-6 mRNA as well as phosphorylated signal transducer and activator of transcription (Stat) 3 expression in the colons of the tumor model mice. These results demonstrate that nicotine suppresses acute colitis and colitis-associated tumorigenesis, and this effect may be associated with the activation of alpha7-nAChR. Furthermore, it is presumed that nicotine downregulates the expression of inflammatory mediators such as IL-6/Stat3 and TNF-alpha, thereby reducing the colonic tumorigenesis associated with chronic colitis. |
