IFN-c is essential for the inhibition of B16BL6 melanoma lung metastasis in chronic alcohol drinking mice
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Hui Zhang Zhaohui Zhu Jenifer M. McKinley Gary G. Meadows
- چاپ و سال / کشور: 2011
Description
We previously found that chronic alcohol consumption (20% w/v in drinking water) that models the level consumed by human alcoholics, when administered to female C57BL/6 mice inhibits B16BL6 melanoma metastasis to the lung; however, the mechanism is not known. Chronic alcohol consumption increases IFN-c producing NK, NKT, CD4?, and CD8? T cells. To examine the impact of IFN-c on metastasis, we inoculated B16BL6 melanoma cells i.v. into control and chronic alcohol drinking IFN-c knockout (KO) mice. Knockout of the ifn-c gene abrogated the anti-metastatic effects associated with alcohol consumption. We examined metastasis in common gamma-chain (cC) KO mice, which are deficient in NK, NKT and CD8? T cells, and in Va14Ja281-/- KO mice, which are deficient in invariant NKT (iNKT) cells, in order to assess the importance of specific IFN-c producing cell types to this effect. We found that the antimetastatic effect of alcohol was still present in cC KO mice and also in cC KO mice depleted of Gr-1? cells. Knockout of iNKT cells reduced the degree but not the antimetastatic effect associated with alcohol. These results indicate that the antimetastatic effect induced by chronic alcohol consumption is IFN-c dependent and that multiple IFN-c producing cell types contribute to this effect.
Clin Exp Metastasis (2011) 28:301–307 DOI 10.1007/s10585-011-9372-1 Received: 18 November 2010 / Accepted: 30 December 2010 / Published online: 14 January 2011
