The immunosuppressive effect of gossypol in mice is mediated by inhibition of lymphocyte proliferation and by induction of cell apoptosis  

作　　者：Wen-bin XU Li-hui XU Hong-song LU Dong-yun OU-YANG Huan-jing SHI Jing-fang DI Xian-hui HE 

机构地区：[1]Institute of Tissue Transplantation and Immunology [2]Institute of Bioengineering, College of Life Science and Technology, Ji-nan University, Guangzhou 510632, China

出　　处：《Acta Pharmacologica Sinica》2009年第5期597-604,共8页中国药理学报（英文版）

基　　金：Acknowledgments This work was supported by the National Natural Science Foundation of China （No 30572199, No 30230350, No 30371651） and the Key Subject of Biochemistry and Molecular Biology of Guangdong Province. We thank Prof 03-xuan XIE for her kind help in capturing images; Dr Xi-chao WANG for performing the flow cytometry analysis; Chun-yong LIU, Xiao-ying WANG, He GUO, 03 GAO, and Yu-ting LI for their excellent technical assistance; and Zhi YANG and Man-lin YAO for kindly helping with preparation of the manuscript.

摘　　要：Aim： To investigate the immunosuppressive effect of gossypol in mice both in vitro and in vivo. Methods： The in vitro effect of gossypol on the proliferation of lymphocytes isolated from lymph nodes of BALB/c mice was determined by CFSE staining and by an MTS assay. Lymphocyte activation and lymphoblastic transformation were evaluated with immunostaining. Cell apoptosis was detected by Annexin-V and Hoechst 33342 staining. The in vivo immunosuppressive effect of gossypol on the DTH reaction was evaluated using a mouse DTH model induced by 2,4-dinitro-1- fluorobenzene （DNFB）. The thickness of the ears was measured, and the histological changes of the mouse auricles were observed after hematoxylin-eosin staining. The proliferation capacity of lymphocytes from DTH mice was also assayed. Results： In vitro, gossypol could significantly inhibit the proliferation of mouse lymphocytes stimulated with phorbol ester plus ionomycin in a dose-dependent manner. Although the expression of the early activation antigen CD69 was not affected, the lymphoblastic transformation of both T and B lymphocyte subsets was significantly suppressed by gossypol. Moreover, gossypol could induce apoptosis of lymphocytes, and the effect was time- and dose-dependent. In vivo, the DTH reaction in mice was markedly alleviated by gossypol injected intraperitoneally. Lymphocytes from drug-treated DTH mice had a reduced proliferation capacity as compared with lymphocytes from untreated DTH mice. Gossypol treatment also markedly reduced the number of infiltrated lymphocytes in the auricles of DTH mice. Conclusion： Gossypol exhibited immunosuppressive effects in mice, probably by inhibition of lymphocyte proliferation and by induction of cell apoptosis.Aim： To investigate the immunosuppressive effect of gossypol in mice both in vitro and in vivo. Methods： The in vitro effect of gossypol on the proliferation of lymphocytes isolated from lymph nodes of BALB/c mice was determined by CFSE staining and by an MTS assay. Lymphocyte activation and lymphoblastic transformation were evaluated with immunostaining. Cell apoptosis was detected by Annexin-V and Hoechst 33342 staining. The in vivo immunosuppressive effect of gossypol on the DTH reaction was evaluated using a mouse DTH model induced by 2,4-dinitro-1- fluorobenzene （DNFB）. The thickness of the ears was measured, and the histological changes of the mouse auricles were observed after hematoxylin-eosin staining. The proliferation capacity of lymphocytes from DTH mice was also assayed. Results： In vitro, gossypol could significantly inhibit the proliferation of mouse lymphocytes stimulated with phorbol ester plus ionomycin in a dose-dependent manner. Although the expression of the early activation antigen CD69 was not affected, the lymphoblastic transformation of both T and B lymphocyte subsets was significantly suppressed by gossypol. Moreover, gossypol could induce apoptosis of lymphocytes, and the effect was time- and dose-dependent. In vivo, the DTH reaction in mice was markedly alleviated by gossypol injected intraperitoneally. Lymphocytes from drug-treated DTH mice had a reduced proliferation capacity as compared with lymphocytes from untreated DTH mice. Gossypol treatment also markedly reduced the number of infiltrated lymphocytes in the auricles of DTH mice. Conclusion： Gossypol exhibited immunosuppressive effects in mice, probably by inhibition of lymphocyte proliferation and by induction of cell apoptosis.

关 键 词：GOSSYPOL LYMPHOCYTES cell proliferation apoptosis delayed-type hypersensitivity 

分 类 号：R285.5[医药卫生—中药学] R512.62[医药卫生—中医学]