Study of gene level for effect of smoking on alveolar macrophage function and lung metastasis of tumor.

吸烟对肺泡巨噬细胞功能及肿瘤肺转移影响的基因水平研究

• 批准号: 09680537
• 负责人: TAKEUCHI Minoru
• 金额: $ 2.3万
• 依托单位: Kyoto Sangyou University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680537/
• 关键词: smoking; alveolar macrophage; tumor; DNA; mRNA; metastasis; mRNA; 転移; 腫瘍; 抗原提示能; 表面抗原; 高タールタバコ; 低タールタバコ; サイトカイン

In previous studies, the effects of smoking on the gene level of alveolar macrophages(AM) immunological functions and lung metastasis of tumor cells are not well defined. In the present study, we investigated the effects of smoking on the gene level of alveolar macrophages immunological functions and lung metastasis of tumor cells in mice. Female C57BL/6 mice were exposed to 20 cigarettes (Coresta Monitor No.2) / day during 10 days using Hamburg II smoking machine. After 10 days, mice were sacrificed. The AM were obtained by brochoalveolar lavage (BAL). The antigen presenting activity of AM was assayed by mixed lymphocyte reaction (MLR). The reactive oxygen species productions in AM were analyzed by flow cytometry using hydroethidine and dichlorofluorescen (DCFH). The expression of surface antigens (Class II and B7-1) of AM were analyzed by flow cytometry. The expressions of IL- 1 β and TNF- α mRNA of gene in AM were analyzed by RT-PCR.The damages of DNA genes were analyzed by 8-OHdG.T … More he lung metastases of tumor cells were assayed by using Lewis lung carcinoma cells(LL/2). The antigen presenting activity of AM was significantly (p<0.01) decreased in smoked mice compared with non-smoked mice. The O_2^- production of AM was significantly (p<0.01) increased in smoked mice, whereas the H_2O_2 production of AM was not difference in both groups. The 8-OHdG levels of DNA in lung tissue were increased in smoked mice. The Class II and B7-1 antigen positive cells in AM were significantly(p<0.01) decreased in smoked mice compared with non-smoked mice. IL-1 β and TNF- α mRNA genes expressions in AM were decrease in smoked mice as compared to non-smoked mice. The metastases to lung of LL/2 tumor cells were promoted in smoked mice compared with non-smoked mice. These results suggest that the antigen presenting activity, expressions of Class II and B7-1 antigens of the AM may be impaired and DNA gene in lung tissue also may be damaged by O_2^- but not H_2O_2 from AM in smoked mice. Less

在以往的研究中，吸烟对肺泡巨噬细胞（AM）基因水平、免疫功能和肿瘤细胞肺转移的影响尚不明确。本研究探讨了吸烟对小鼠肺泡巨噬细胞基因水平、免疫功能及肿瘤细胞肺转移的影响。使用Hamburg II吸烟机，将雌性C57 BL/6小鼠暴露于20支香烟（Coresta Monitor No.2）/天，持续10天。10天后，处死小鼠。支气管肺泡灌洗（BAL）获得AM。混合淋巴细胞反应（MLR）检测AM的抗原提呈活性。用流式细胞仪分析AM中活性氧的产生。流式细胞术检测AM表面抗原（Class II和B7-1）的表达。RT-PCR检测AM中IL- 1 β、TNF- α mRNA的表达，8-OHdG.T检测AM中DNA基因的损伤 ...更多信息 用刘易斯肺癌细胞（LL/2）检测肿瘤细胞的肺转移。吸烟小鼠AM的抗原提呈活性显著低于非吸烟小鼠（P<0.01）。吸烟组小鼠AM产生O_2 ~-的能力显著高于对照组（P<0.01），而H_2O_2的能力与对照组无显著差异。吸烟小鼠肺组织DNA中8-OHdG含量增加。吸烟组AM中Ⅱ类抗原和B7-1抗原阳性细胞数明显低于非吸烟组（P<0.01）。吸烟小鼠AM中IL-1 β和TNF- α mRNA表达较非吸烟小鼠降低。吸烟小鼠的LL/2肿瘤细胞的肺转移较非吸烟小鼠明显增加。提示O_2^-可损伤AM的抗原提呈活性、II类抗原和B7-1抗原的表达及肺组织DNA基因，但H_2O_2对AM的损伤作用不明显。少

项目成果

M.Takeuchi et al: "The number of interleukin-1 (IL-1) receptor on lung fibroblasts in patients with idiopathic pulmonary fibrosis."Respiration. 6. 236-241 (1999)

M.Takeuchi 等人：“特发性肺纤维化患者肺成纤维细胞上白细胞介素 1 (IL-1) 受体的数量。”呼吸。

Rushan Lu et al: "tobacco : The Growing Epidemic"Springer. 998 (2000)

Rushan Lu 等人：“烟草：日益增长的流行病”施普林格。

T.Mikuniya, S.Nagai, M.Takeuchi, T.Mio, Y.Hosono, H.Miki, M.Shigematsu, K.Hamada and T.Izumi: "Significance of the interleukin-1 receptor antagonist/interleukin-1β ratio as a prognostic factor in pulmonary sarcoidosis."Respiration. 67. 389-396 (2000)

T.Mikuniya、S.Nagai、M.Takeuchi、T.Mio、Y.Hosono、H.Miki、M.Shigematsu、K.Hamada 和 T.Izumi：“白细胞介素 1 受体拮抗剂/白细胞介素 1β 比率的意义作为肺结节病的预后因素。“呼吸。67. 389-396 (2000)

M.Takeuchi et.al: "Effect of soft X-ray irradiation on NK cell activity and the percentage of asialo GM-1 positive cells in spleen cells of mice"J.Vet.Med.Sci. 59. 413-414 (1997)

M.Takeuchi等人：“软X射线照射对小鼠脾细胞NK细胞活性和asialo GM-1阳性细胞百分比的影响”J.Vet.Med.Sci。

A.K.Varma et al: "Tobacco Counters Health"Macmillan India Ltd.. 197 (2000)

A.K.Varma 等人：“烟草对抗健康”Macmillan India Ltd.. 197 (2000)