摘要
The signal transducers and activators of transcription (STATs) have diverse biological functions and are involved in cell differentiation, proliferation, development, apoptosis and inflammation. Several constitutively activated STATs have been observed in a wide variety of human cancer cell lines and primary tumor cells, including blood malignancies and solid neoplasias. Although regulatory T (Treg) cells induce immune tolerance by suppressing host immune responses against selfor nonself-antigens, thus playing critical roles in preventing autoimmune diseases, they might inhibit antitumor im-munity and promote tumor growth. Our previous findings suggest that the supernatant from STAT4silenced tumor cell culture can significantly increase the ratio of CD4+ CD25+ Foxp3+ regulatory T cells among splenic cells in vitro, when compared to that from normal tumor cell culture. In the present study, we identified that the mouse lymphoma cell line EL-4 expressed a high level of STAT4, and silencing of STAT4 by siRNA did not change the expression levels of TGF-β and IL-10 in EL-4 cells. Two-dimensional electrophoresis was conducted to examine the difference of expression profiles of proteins between normal and STAT4-silenced EL4 cells. Some of the protein which has been changed may induce CD4+ CD25+ Foxp3+ regulatory T cells in vitro.
The signal transducers and activators of transcription （STATs） have diverse biological functions and are involved in cell differentiation, proliferation, development, apoptosis and inflammation. Several constitutively activated STATs have been observed in a wide variety of human cancer cell lines and primary tumor cells, including blood malignancies and solid neoplasias. Although regulatory T （Treg） cells induce immune tolerance by suppressing host immune responses against self- or nonself-antigens, thus playing critical roles in preventing autoimmune diseases, they might inhibit antitumor immunity and promote tumor growth. Our previous findings suggest that the supernatant from STAT4-silenced tumor cell culture can significantly increase the ratio of CD4^＋ CD25^＋ Foxp3^＋ regulatory T cells among splenic cells in vitro, when compared to that from normal tumor cell culture. In the present study, we identified that the mouse lymphoma cell line EL-4 expressed a high level of STAT4, and silencing of STAT4 by siRNA did not change the expression levels of TGF-β and IL-10 in EL-4 cells. Two-dimensional electrophoresis was conducted to examine the difference of expression profiles of proteins between normal and STAT4-silenced EL4 cells. Some of the protein which has been changed may induce CD4^＋ CD25^＋ Foxp3^＋ regulatory T ceils in vitro.
基金
Supported by the National Key Basic Research and Development Program of China (Grant No. 2007CB914804)
National High Technology Research and Development Program of China (Grant No. 2007AA021010)
Foundation of the Ministry of Education of China for Returned Scholars
Key Project of the Science & Technology Pillar Program of Tianjin (Grant No. 07ZCKFSH03700)
Innovative Research Foundation of Nankai University
