Liyun Gu

Publications (3)12.82 Total impact

• Article: Selective Sequestration of STAT1 in the Cytoplasm via Phosphorylated SHP-2 Ameliorates Murine Experimental Colitis.

  Xingxin Wu, Wenjie Guo, Limei Wu, Yanhong Gu, Liyun Gu, Suhai Xu, Xuefeng Wu, Yan Shen, Yuehai Ke, Renxiang Tan, Yang Sun, Qiang Xu
  [show abstract] [hide abstract]
  ABSTRACT: The side effects of current immunosuppressive drugs have impeded the development of therapies for immune diseases. Selective regulation of STAT signaling is an attractive strategy for treating immune disorders. In this study, we used a small-molecule compound to explore possible means of targeting STAT1 for the treatment of Th1-mediated inflammation. Selective regulation of STAT1 signaling in T cells from C57BL/6 mice was accomplished using fusaruside, a small-molecule compound that triggers the tyrosine phosphorylation of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2). The interaction of tyrosine phosphorylated SHP-2 (pY-SHP-2) with cytosolic STAT1 prevented the recruitment of STAT1 to IFN-γR and specifically inhibited STAT1 signaling, resulting in a reduction in Th1 cytokine production and an improvement in 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside, resulting in STAT1 activation and worsened colitis. The fusaruside-induced ability of pY-SHP-2 to selectively sequestrate STAT1 from recruitment to the receptor is independent of its function as a phosphatase, demonstrating a novel role for SHP-2 in regulating both STAT1 signaling and Th1-type immune responses. These findings could lead to increased options for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases.
  The Journal of Immunology 08/2012; 189(7):3497-507. · 5.79 Impact Factor
• Article: Erlotinib inhibits T-cell-mediated immune response via down-regulation of the c-Raf/ERK cascade and Akt signaling pathway.

  Qiong Luo, Yanhong Gu, Wei Zheng, Xingxin Wu, Fangyuan Gong, Liyun Gu, Yang Sun, Qiang Xu
  [show abstract] [hide abstract]
  ABSTRACT: Erlotinib is a potent inhibitor of epidermal growth factor receptor tyrosine kinase and has been demonstrated to treat advanced or metastatic non-small cell lung cancer to prolong survival after failure of first-line or second-line chemotherapy. However, little is known about its effects on immune system. In the present study, we aimed to investigate the immunosuppressive activity of erlotinib on T lymphocytes both in vitro and in vivo, and further explore its potential molecular mechanism. Erlotinib exerted a significant inhibition on the T cell proliferation and activation induced by concanavalin A, anti-CD3 plus anti-CD28, staphylococcal enterotoxin B or phorbol myristate acetate respectively in a concentration-dependent manner and it also inhibited the secretion of the proinflammatory cytokines such as IL-2 and IFN-γ of activated T cells. Further study showed that erlotinib caused G0/G1 arrest and suppressed the phosphorylations of c-Raf, ERK and Akt in activated T cells. Moreover, erlotinib significantly ameliorated picryl chloride-induced ear contact dermatitis in a dose-dependent manner in vivo. In summary, these findings suggest that erlotinib may cause the impairment of T-cell-mediated immune response both in vitro and in vivo through inhibiting T cell proliferation and activation, which is closely associated with its potent down-regulation of the c-Raf/ERK cascade and Akt signaling pathway.
  Toxicology and Applied Pharmacology 03/2011; 251(2):130-6. · 4.45 Impact Factor
• Article: Jaceosidin inhibits contact hypersensitivity in mice via down-regulating IFN-γ/STAT1/T-bet signaling in T cells.

  Ye Yin, Yang Sun, Liyun Gu, Wei Zheng, Fangyuan Gong, Xingxin Wu, Yan Shen, Qiang Xu
  [show abstract] [hide abstract]
  ABSTRACT: In the present study, we aimed to investigate the immunosuppressive activity of jaceosidin, a flavone isolated from Artemisia vestita, on T lymphocytes both in vitro and in vivo, and further explore its potential molecular mechanism. Jaceosidin exerted a significant inhibition on the T cell proliferation and activation induced by concanavalin A (Con A) in a concentration-dependent manner and it also inhibited the secretion of the proinflammatory cytokines such as IL-2, TNF-α and IFN-γ of activated T cells. Further study showed that jaceosidin down-regulated STAT1 activation and T-bet expression in activated T cells. Moreover, in order to investigate the immunosuppressive effect of jaceosidin in vivo, the picryl chloride (PCl)-induced ear contact dermatitis model was performed on BALB/c mice. Jaceosidin significantly ameliorated PCl-induced ear swelling in a dose-dependent manner, which was due to its inhibition of the STAT1/T-bet signaling pathway. In summary, these findings suggest that jaceosidin exerts its immunosuppressive effect both in vitro and in vivo through inhibiting T cell proliferation and activation, which is closely associated with its potent down-regulation of the IFN-γ/STAT1/T-bet signaling pathway.
  European journal of pharmacology 01/2011; 651(1-3):205-11. · 2.59 Impact Factor