Kang Hee, Choi Tae-Won, Ahn Kyoo-Seok, Lee Ju-Young, Ham In-Hye, Choi Ho-Young, Shim Eun-Sheb, Sohn Nak-Won
Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyunghee University, 1 Seochungdong, Yongin, South Korea.
J Ethnopharmacol. 2009 May 4;123(1):6-14. doi: 10.1016/j.jep.2009.02.045. Epub 2009 Mar 9.
So-Shi-Ho-Tang (SSHT) or known as Sho-Saiko-To in Japanese and Xiao-Chai-Hu-Tang in Chinese has been used to treat chronic liver disease and other infections, and its hepatoprotective effects have been widely studied.
We tried to investigate the immunomodulatory effect of SSHT on interferon (IFN)-gamma and interleukin (IL)-4 and their Th1/Th2 transcription factors in vivo and in vitro since these two cytokines are important in determining the type of cell-mediated inflammatory and humoral responses.
SSHT was orally given to BALB/c mice for 7 days and then injected with anti-CD3 mAb intravenously. IFN-gamma, IL-4, IL-2 and Th1/Th2-specific transcription factors as well as splenocyte subsets were measured. Splenocytes and CD4 T cells were cultured with anti-CD3 or anti-CD3/anti-CD28 in the presence of SSHT, its constituent herbs and baicalin, and the levels of cytokines and transcription factors were measured by ELISA and western blotting.
Oral administration of SSHT to mice in response to i.v. anti-CD3 injection enhanced the expression of IFN-gamma, IL-4 and IL-2 in the serum and spleen at the secreted protein and mRNA level. This was accompanied by the upregulation of CD69 and CD4 T cell populations by flow cytometry. The upregulation of IFN-gamma and IL-4 by SSHT did not occur in anti-CD3/anti-CD28 stimulated CD4 T cells in vitro. However, SSHT was capable of producing the cytokines in anti-CD3 stimulated splenocytes even in the absence of CD28, suggesting a role for some soluble factors produced by antigen presenting cells (APC). In support of this, we found that SSHT increased IL-12 and IL-6 in the same cells. STAT4, but not T-bet, was involved in the upregulation of IFN-gamma by SSHT while the increased IL-4 expression was accompanied by a parallel increase in c-Maf but independent of STAT6 and GATA-3.
These data indicate that the upregulation of IFN-gamma and IL-4 by SSHT must occur through some interactions between APC and CD4 T cells. Taken together, the present data provide additional information on some of the immunological mechanisms of SSHT for treatment of liver diseases and infections.
柴胡桂枝汤（SSHT），在日语中称为小柴胡汤（Sho - Saiko - To），在中文中称为小柴胡汤（Xiao - Chai - Hu - Tang），已被用于治疗慢性肝病和其他感染，其肝脏保护作用已得到广泛研究。
我们试图研究柴胡桂枝汤在体内和体外对干扰素（IFN）-γ和白细胞介素（IL）-4及其Th1/Th2转录因子的免疫调节作用，因为这两种细胞因子在决定细胞介导的炎症和体液反应类型中很重要。
将柴胡桂枝汤口服给予BALB/c小鼠7天，然后静脉注射抗CD3单克隆抗体。检测IFN -γ、IL -4、IL -2和Th1/Th2特异性转录因子以及脾细胞亚群。脾细胞和CD4 T细胞在柴胡桂枝汤、其组成草药和黄芩苷存在的情况下，用抗CD3或抗CD3/抗CD28进行培养，并用ELISA和western blotting检测细胞因子和转录因子的水平。
对静脉注射抗CD3的小鼠口服柴胡桂枝汤，在分泌蛋白和mRNA水平上增强了血清和脾脏中IFN -γ、IL -4和IL -2的表达。通过流式细胞术检测发现，这伴随着CD69和CD4 T细胞群体的上调。在体外，柴胡桂枝汤对抗CD3/抗CD28刺激的CD4 T细胞未上调IFN -γ和IL -4。然而，即使在没有CD28的情况下，柴胡桂枝汤也能够在抗CD3刺激的脾细胞中产生细胞因子，这表明抗原呈递细胞（APC）产生的某些可溶性因子发挥了作用。支持这一点的是，我们发现柴胡桂枝汤在相同细胞中增加了IL -12和IL -6。STAT4而非T - bet参与了柴胡桂枝汤对IFN -γ的上调，而IL -4表达的增加伴随着c - Maf的平行增加，但与STAT6和GATA -3无关。
这些数据表明，柴胡桂枝汤对IFN -γ和IL -4的上调一定是通过APC和CD4 T细胞之间的某些相互作用发生的。综上所述，本研究数据为柴胡桂枝汤治疗肝病和感染的一些免疫机制提供了更多信息。
