T‐bet is a new synergistic meeting point for the BCR and TLR9 signaling cascades

The importance of the BCR and TLR9 in autoimmunity and in the production of auto‐antibodies is well established but the underlying molecular mechanism still needs to be determined. Here, we aim to characterize the BCR‐TLR9 cross‐talk by its effect on T‐bet, as T‐bet is activated and regulated by both receptors and has an important role in class‐switching to pathological IgG2a in mice. Using primary mouse B cells, we demonstrate that T‐bet expression is synergistically elevated by the cross‐talk between the BCR and TLR9. To test the effect of this synergy on IgG2a‐switching, the levels of switched B cells were checked by functional tests. We found that BCR costimulation had no additional effect on TLR9‐induced IgG2a expression, however the expression of Rad51 was synergistically increased. To check the biological significance of the synergy, we compared T‐bet expression in B cells from healthy and collagen‐induced arthritis mice but no differences were found. Taken together, we demonstrate here that signaling cascades driven by the BCR and TLR9 have a newly identified meeting point at T‐bet. The two cascades act synergistically on T‐bet; however additional signals may be needed to induce prolonged functional responses such as class‐switch recombination.     

加减龙胆泻肝汤治疗带下病湿热下注的临床研究

目的:探讨加减龙胆泻肝汤治疗带下病湿热下注型患者的临床疗效及其应用价值。方法:选取于2010年7月1日～2013年1月1日在我院收治的带下病湿热下注型患者80例。将患者随机分配为中药治疗组与西药对照组,每组40例患者。同时保证患者具有大致相同的既往病史。中药治疗组采用加减龙胆泻肝汤的治疗方式;而西药对照组,则根据患者阴道感染的种类选择正确的药物治疗。其中对照组中40例患者均为细菌性阴道感染,则采用甲硝唑治疗。对比两种治疗方法的临床效果,并讨论其应用价值。结果:中药治疗组显效13例,有效25例,无效2例,有效率为95.00%;西药对照组显效20例,有效15例,无效5例,有效率为87.50%。同时两组患者带下病症状均得到良好改善,差异无统计学意义(P>0.05)。结论:运用加减龙胆泻肝汤治疗带下病湿热下注型患者,与西药治疗疗效相当,临床效果显著,值得广泛应用及推广。     

Antimetastatic effects of thalidomide by inducing the functional maturation of peripheral natural killer cells

Thalidomide and its analogues are known as immunomodulatory drugs (IMiDs) that possess direct antimyeloma effects, in addition to other secondary effects, including antiangiogenic, antiinflammatory, and immunomodulatory effects. Although the involvement of natural killer (NK) cells in the antitumor effects of IMiDs has been reported, it is unclear whether IMiDs inhibit cancer cell metastasis by regulating the antitumor function of NK cells. In this study, we examined the protective effects of thalidomide against cancer metastasis by focusing on its immunomodulatory effects through NK cells. Using experimental lung metastasis models, we found that pharmacological effects of thalidomide on host cells, but not its direct anticancer tumor effects, are responsible for the inhibition of lung metastases. To exert the antimetastatic effects of thalidomide, both γ‐interferon (IFN‐γ) production and direct cytotoxicity of NK cells were essential, without notable contribution from T cells. In thalidomide‐treated mice, there was a significant increase in the terminally differentiated mature CD27^lo NK cells in the peripheral tissues and NK cells in thalidomide‐treated mice showed significantly higher cytotoxicity and IFN‐γ production. The NK cell expression of T‐bet was upregulated by thalidomide treatment and the downregulation of glycogen synthase kinase‐3β expression was observed in thalidomide‐treated NK cells. Collectively, our study suggests that thalidomide induces the functional maturation of peripheral NK cells through alteration of T‐bet expression to inhibit lung metastasis of cancer cells.     

糖皮质激素对哮喘豚鼠肺组织T-bet基因表达的影响

目的 探讨哮喘豚鼠肺组织中T-bet基因m-RNA的表达水平，并观察了糖皮质激素对T-bet基因表达的调节作用。方法 采用RT-PCR技术，检测哮喘豚鼠肺组织中T-bet基因表达水平及糖皮质激素对该基因表达的影响。结果 哮喘组肺组织中T-bet基因的表达水平较低，经糖皮质激素干预后哮喘豚鼠肺组织中T-bet基因的表达水平显著增高。糖皮质激素治疗组肺组织中T-bet基因的表达水平和哮喘组间有显著性差异（P〈0．001）。结论 糖皮质激素可上调哮喘豚鼠肺组织中T-bet基因表达水平低下。