Study on the mechanism of chemokine release from mast cells by environmental chemicals

环境化学物质肥大细胞释放趋化因子机制研究

• 批准号: 12672182
• 负责人: TESHIMA Reiko
• 金额: $ 2.3万
• 依托单位: National Institute of Health Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672182/
• 关键词: Mast cells; Environmental chemicals; Hydroquinone; Chemokine; Gene expression; nitrogenous pesticide; Ca^<2+> signals; ハイドロキシン; フタル酸エステル; カルシウム応答; 情報伝達

The effect of the anti-oxidant and Ca^<2+> ATPase inhibitor, 2,5-di-(tert-butyl)-1, 4-hydroquinone (DTBHQ), on the release of MCP-1 from RBL-2H3 and bone marrow-derived mast cells (BMMCs) were investigated. DTBHQ increased the intracellular free Ca^<2+> concentration and induced MCP- 1 release in a dose-dependent manner. It was inhibited by treatment with actinomycin D, cyclosporin A, and p38 MAP kinase inhibitor SB202190. Furthermore, RT-PCR showed a time-dependent increase of MCP-1 mRNA. Thus MCP-1 release seems to depend on Ca^<2+>-dependent transcriptional activation. Next, the mRNA expression profiles (8,799 genes) of RBL-2H3 cells activated by 10μM DTBHQ were analyzed with GeneChip arrays. The genes, including MCP-1, GADD45, Relaxin HI, IL-3, IL-4, IL-9, IL-13, GADD153, were significantly up-regulated by DTBHQ. These results suggest that DTBHQ seems to induce proinflammatory responses by stimulating the production of chemokine and several cytokines through the expression of several transcription factors.

研究了抗氧化剂和Ca^2+ ATP酶抑制剂2，5-二叔丁基-1，4-氢醌（DTBHQ）对RBL-2 H3和骨髓源性肥大细胞（BMMCs）释放MCP-1的影响。DTBHQ以剂量依赖性方式增加细胞内游离Ca^<2+>浓度并诱导MCP- 1释放。放线菌素D、环孢菌素A和p38 MAP激酶抑制剂SB 202190可抑制该作用。RT-PCR显示MCP-1 mRNA表达呈时间依赖性增加。因此，MCP-1的释放似乎依赖于Ca^<2+>依赖的转录激活。接下来，用基因芯片阵列分析了10μM DTBHQ激活的RBL-2 H3细胞的mRNA表达谱（8，799个基因）。DTBHQ可显著上调MCP-1、GADD 45、Relaxin HI、IL-3、IL-4、IL-9、IL-13、GADD 153等基因表达。这些结果表明，DTBHQ似乎通过刺激趋化因子和几种细胞因子的产生，通过几种转录因子的表达诱导促炎反应。

项目成果

R. Nakamura, R.Teshima, J.Sawada: "Effect of dialkyl phthalates on the degranulation and Ca2+ response of RBL-2H3 mast cells"Immunol. Lett.. 80. 119 (2002)

R. Nakamura、R.Teshima、J.Sawada：“邻苯二甲酸二烷基酯对 RBL-2H3 肥大细胞脱颗粒和 Ca2 反应的影响”免疫学。

R.Teshima, J. Onose, H. Okunuki, J.Sawada: "Effect of Ca^<2+> ATPase inhibitors on MCP- 1 release from bone marrow-derived mast cells and the involvement of p38 MAP kinase activation"Int. Arch.Allergy Immunol.. 121. 34 (2000)

R.Teshima、J. Onose、H. Okunuki、J.Sawada：“Ca^2 ATP酶抑制剂对骨髓源性肥大细胞MCP-1释放的影响以及p38 MAP激酶激活的参与”Int。

R.Nakamura, S.Ishida, S.Ozawa, Y. Saito, H.Okunuki, R.Teshima, J.Sawada: "Gene expression profiling of Ca^<2+>-atpase inhibitor DTBHQ and antigen-stimulated RBL-2H3 mast cells"Inflamm Res. 51. 611 (2002)

R.Nakamura、S.Ishida、S.Ozawa、Y. Saito、H.Okunuki、R.Teshima、J.Sawada：“Ca^<2>-atpase 抑制剂 DTBHQ 和抗原刺激的 RBL-2H3 肥大的基因表达谱

Reiko Teshima: "Effect of Ca^<2+> ATPase inhibitors on MCP-1 release from bone-marrow-derived mast cells and the involvement of p38Map kinase activation"Int.Arch.Allergy Immunol.. 121. 34-43 (2000)

Reiko Teshima：“Ca ^ 2 ATP酶抑制剂对骨髓源性肥大细胞MCP-1释放的影响以及p38Map激酶激活的参与”Int.Arch.AllergyImmunol..121.34-43(2000)

中村 亮介: "Affymetrix GeneChipを用いた遺伝子発現解析"ImmunoToxLett.. 6(2). 8-10 (2001)

Ryosuke Nakamura：“使用 Affymetrix GeneChip 进行基因表达分析”ImmunoToxLett.. 6(2) (2001)。