Antimetastatic effect of an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis strain Aoyama B, Z-100, through the production of interleukin-12.
Antimetastatic effect of an immunomodulatory arabinomannan extracted from Mycobacterium tuberculosis strain Aoyama B, Z-100, through the production of interleukin-12.
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从结核分枝杆菌菌株 Aoyama B, Z-100 中提取的免疫调节性阿拉伯甘露聚糖通过产生 IL-12 具有抗转移作用。
DOI：
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发表时间：
2003
影响因子：
2
通讯作者：
M. Takei
中科院分区：
文献类型：
--
作者：
H. Oka;Y. Shiraishi;H. Sasaki;K. Yoshinaga;Y. Emori;M. Takei
本研究利用野生型C57BL/6小鼠或IL-12p40敲除（IL-12p40 KO）小鼠接种高转移性B16F10黑色素瘤，研究白细胞介素(IL)-12对Z-100抗转移作用的影响。当C57BL/6小鼠接种B16F10黑色素瘤（2 × 10(5)个细胞/小鼠腹腔注射）后，接种14 d后，Z-100 （10 mg/kg腹腔注射）显著抑制了B16F10黑色素瘤的肺转移。另一方面，在接种B16F10黑色素瘤的IL-12p40 KO小鼠中，未观察到Z-100的抗转移作用。这些结果表明，IL-12是Z-100抗转移作用出现的必要条件。由于已有报道称辅助性T (Th) 2细胞应答在肿瘤转移中起作用，因此我们研究了Z-100对Th1/Th2细胞应答免疫平衡的调节作用。在携带B16F10黑色素瘤的C57BL/6小鼠和IL-12p40 KO小鼠中，与正常小鼠相比，Th1细胞因子（IL-2，干扰素- γ）的产生均被显著抑制。另一方面，这些小鼠的Th2细胞因子（IL-4, IL-10）的产生增加。在携带B16F10黑色素瘤的C57BL/6小鼠中给予Z-100 （10 mg/kg i.p）可改善Th1/Th2细胞反应的平衡，从Th2优势状态恢复到正常状态。然而，在携带相同肿瘤的IL-12p40 KO小鼠中，未观察到Z-100对Th1/Th2细胞反应的改善。此外，在体外实验中，Z-100显著增加巨噬细胞产生IL-12，并呈浓度依赖性，而Z-100显著降低巨噬细胞产生IL-10。这些结果表明，Z-100上调IL-12的产生，下调IL-10的产生，与改善Th1/Th2细胞从Th2优势状态到正常状态，从而抑制肿瘤转移有关。
In this study, the role of interleukin (IL)-12 on the antimetastatic effect of Z-100 was investigated using wild-type C57BL/6 mice or IL-12p40 knockout (IL-12p40 KO) mice inoculated with highly metastatic B16F10 melanoma. When C57BL/6 mice were inoculated with B16F10 melanoma (2x10(5) cells/mouse i.v.), Z-100 (10 mg/kg i.p.) significantly suppressed the pulmonary metastasis of B16F10 melanoma 14 d after tumor inoculation. On the other hand, the antimetastatic effect of Z-100 was not observed in IL-12p40 KO mice inoculated with B16F10 melanoma. These results indicate that IL-12 is essentially required for the appearance of the antimetastatic effect of Z-100. Since helper T (Th) 2 cell responses have been reported to have a role in tumor metastasis, the regulatory effect of Z-100 on the immune balance of Th1/Th2 cell responses was investigated. In both C57BL/6 mice and IL-12p40 KO mice bearing B16F10 melanoma, Th1 cytokine production (IL-2, interferon-gamma) was significantly suppressed as compared with those in normal mice. On the other hand, Th2 cytokine production (IL-4, IL-10) in these mice was increased. The administration of Z-100 (10 mg/kg i.p.) in C57BL/6 mice bearing B16F10 melanoma improved the balance of Th1/Th2 cell responses from the Th2-dominant state to the normal state. However, the improvement of Th1/Th2 cell responses by Z-100 was not observed in IL-12p40 KO mice bearing the same tumors. In addition, Z-100 significantly increased IL-12 production by macrophages in a concentration-dependent manner, while Z-100 significantly decreased IL-10 production by these cells in vitro. These results suggested that up-regulation of IL-12 production and down-regulation of IL-10 production by Z-100 are related to the improvement of Th1/Th2 cell responses from the Th2-dominant state to the normal state, which resulted in suppression of tumor metastasis.
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影响因子：
4.4
作者：
B. Perussia;S. Chan;Annalisa D'Andrea;K. Tsuji;D. Santoli;M. Pospíšil;D. Young;S. Wolf;Giorgio Trinchieri
通讯作者：
B. Perussia;S. Chan;Annalisa D'Andrea;K. Tsuji;D. Santoli;M. Pospíšil;D. Young;S. Wolf;Giorgio Trinchieri
影响因子：
4.4
作者：
S. Wolf;P. Temple;Michiko Kobayashi;D. Young;M. Dicig;L. Lowe;R. Dzialo;L. Fitz;C. Ferenz;R. Hewick
通讯作者：
S. Wolf;P. Temple;Michiko Kobayashi;D. Young;M. Dicig;L. Lowe;R. Dzialo;L. Fitz;C. Ferenz;R. Hewick
人朗格汉斯细胞合成 IL-12。
DOI：
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发表时间：
1996
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kang,K;Kubin,M;Cooper,KD;Lessin,SR;Trinchieri,G;Rook,AH
通讯作者：
Rook,AH
影响因子：
4.4
作者：
S. Swain;A. Weinberg;M. English;G. Huston
通讯作者：
S. Swain;A. Weinberg;M. English;G. Huston
γ-干扰素在 T 细胞诱导的肿瘤消退中发挥着关键作用。
影响因子：
11.2
作者：
Tuttle,TM;McCrady,CW;Inge,TH;Salour,M;Bear,HD
通讯作者：
Bear,HD