RemX Specialty Staffing, c/o Altria Client Services, Research, Development & Engineering, 601 East Jackson Street, Richmond, VA 23219, USA.
Int Immunopharmacol. 2010 Sep;10(9):1029-40. doi: 10.1016/j.intimp.2010.06.002. Epub 2010 Jun 22.
Moist smokeless tobacco use is associated with various types of oral injury, including leukoplakia and dipper's pouch, although the mechanism by which the injury is caused still remains unclear. One possible mechanism is that moist smokeless tobacco affects the inflammatory response. For example, a study by Johnson et al. demonstrated a reduction in the volume density of macrophages and increased inflammation and redness at the smokeless tobacco placement site when compared to non-placement site. The current study investigated the direct effect of reference moist smokeless tobacco extract (STE) exposure on the viability of MM6 monocyte/macrophage cell line. The exposure of MM6 cells to various concentrations of STE, led to a significant and dose-related decrease in cell viability. Furthermore, STE exposure resulted in an increase in Annexin V/PI positive cells, an increase in TUNEL-positive cells, and cleaved PARP staining all of which were inhibited by pre-incubation with a pan-caspase inhibitor, suggesting that the observed STE toxicity was due to the induction of apoptosis. Next, the role of various moist smokeless tobacco-derived components in STE-induced apoptosis of MM6 cells was investigated. Our findings suggest that STE-induced osmotic stress, but not exposure to nicotine, plays an important role in STE-induced apoptosis of MM6 cells. Together, these data show for the first time that STE exposure leads to the induction of apoptosis in human monocyte/macrophage cells, which appears to be induced in part, by reference STE-mediated osmotic stress.
使用湿润型无烟气烟草与各种口腔损伤有关，包括口腔白斑病和烟袋，尽管其造成损伤的机制仍不清楚。一种可能的机制是湿润型无烟气烟草影响炎症反应。例如，Johnson 等人的研究表明，与非放置部位相比，湿润型无烟气烟草放置部位的巨噬细胞体积密度降低，炎症和红肿增加。本研究调查了参考湿润型无烟气烟草提取物（STE）暴露对 MM6 单核/巨噬细胞系活力的直接影响。MM6 细胞暴露于不同浓度的 STE 导致细胞活力显著且剂量相关下降。此外，STE 暴露导致 Annexin V/PI 阳性细胞增加，TUNEL 阳性细胞增加，以及切割的 PARP 染色增加，所有这些均被泛半胱天冬酶抑制剂的预孵育所抑制，表明观察到的 STE 毒性是由于诱导细胞凋亡所致。接下来，研究了各种湿润型无烟气烟草衍生成分在 STE 诱导的 MM6 细胞凋亡中的作用。我们的研究结果表明，STE 诱导的渗透压应激，而不是暴露于尼古丁，在 STE 诱导的 MM6 细胞凋亡中起着重要作用。总之，这些数据首次表明，STE 暴露导致人单核/巨噬细胞细胞凋亡，这部分似乎是由参考 STE 介导的渗透压应激诱导的。
