2-(1H-Benzimidazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol,a Benzimidazole Derivative, Inhibits T Cell Proliferation Involving H+/K+-ATPase Inhibition

Molecules

Xing-Yan Luo¹  Jin Liu¹  Li-Mei Li¹  Ning Li¹  Yan-Tang Wang¹  Min-Hui Li¹  Si-Nian Liu¹  Tai Yang¹  Ning Huang¹  Yang Liu¹  Qiang Zou¹  Hua Li² 

[1] Department of Immunology, Chengdu Medical College, Chengdu 610500, China;Department of Oncology, Chengdu Military General Hospital, Chengdu 610083, China;

关键词: benzimidazole derivative;    T cell proliferation;    H+/K+-ATPases;    immunomodulatory;   

DOI  :  10.3390/molecules191117173

来源: DOAJ

【 摘 要 】

In this study, a benzimidazole derivative named BMT-1 is revealed as a potential immunomodulatory agent. BMT-1 inhibits the activity of H+/K+-ATPases from anti-CD3/CD28 activated T cells. Furthermore, inhibition the H+/K+-ATPases by use of BMT-1 should lead to intracellular acidification, inhibiting T cell proliferation. To explore this possibility, the effect of BMT-1 on intracellular pH changes was examined by using BCECF as a pH-dependent fluorescent dye. Interestingly, increases in the pHi were observed in activated T cells, and T cells treated with BMT-1 showed a more acidic intracellular pH. Finally, BMT-1 targeted the H+/K+-ATPases and inhibited the proliferative response of anti-CD3/CD28-stimulated T cells. A cell cycle analysis indicated that BMT-1 arrested the cell cycle progression of activated T cells from the G1 to the S phase without affecting CD25 expression or interleukin-2 (IL-2) production; treatingIL-2-dependent PBMCs with BMT-1 also led to the inhibition of cell proliferation. Taken together, these findings demonstrate that BMT-1 inhibits the proliferation of T cells by interfering with H+/K+-ATPases and down-regulating intracellular pHi. This molecule may be an interesting lead compound for the development of new immunomodulatory agents.

【 授权许可】

Unknown