[The role of MAPK signal transduction pathway in killing tumor cells by Mtb-Ag activated gammadelta T cells].
作者:
Hu(Jian-Guo),Hou(Yan-Qiang),Li(Bai-Qing)
状态:
发布时间2005-01-04
, 更新时间 2016-11-24
期刊:
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
摘要:
To explore the role of MAPK signal transduction pathway in killing tumor cells by Mycobacteria tuberculosis antigen (Mtb-Ag) activated human gammadeltaT cells.,Normal human peripheral blood mononuclear cells (PBMCs) were stimulated with Mtb-Ag and expanded in rIL-2-containing medium to induce gammadeltaT cells. The highly purified gammadeltaT cells were isolated by positive selection with MACS separator. Proportion of gammadeltaT cells was detected by flow cytometry (FCM). The cytotoxicity and CD69 expression of gammadeltaT cells pre-treated with or without PD98059 (Erk inhibitor) or SB203580 (p38 inhibitor) were detected by MTT colorimetry assay and FCM, respectively.,The percentages of gammadeltaT cells in freshly isolated PBMCs, Mtb-Ag-activated PBMCs and cells sorted by MACS were 3.56%, 74.63% and 98.20%, respectively. The cytotoxicities of gammadeltaT cells to tumor cell lines (K562 and Raji cells) were inhibited by PD98059. The inhibitory rate of cytotoxicity to K562 cells by gammadeltaT cells (39.27%) was higher than that to Raji cells(26.58%). CD69 expressions on gammadeltaT cells induced by K562 or Raji cells were decreased by pretreatment with 100 mumol/L of PD98059. But SB203580 had no effects on the cytotoxicity and CD69 expression on gammadeltaT cells induced by K562 and Raji cells.,Erk MAPK pathway, not p38 MAPK, plays an important role in triggering cytotoxicity of gammadeltaT cells. The Erk pathway may affect on the granule exocytosis of gammadeltaT cells more than the Fas/FasL-mediated cytotoxicity of gammadeltaT cells. Moreover, Erk MAPK pathway is also involved in expression of activation molecule CD69 on gammadeltaT cells induced by tumor cells.