Inhibiting effect of Astragalus polysaccharides on the functions of CD4+CD25 highTreg cells in the tumor microenvironment of human hepatocellular carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Astragalus polysaccharides (APS), the main active extract from Astragalus membranaceus (a traditional Chinese medicinal herb), is associated with a variety of immunomodulatory activities. The purpose of the present study was to examine the effect of APS on the function of Treg cells in the tumor microenvironment of human hepatocellular carcinoma (HCC) and to identify the pharmacologic mechanism of APS responsible for the anti-chemotactic activity in CD4+CD25highTreg cells in tumor site of HCC.</p><p><b>METHODS</b>The prevalence of Treg in fresh tissue samples from 31 patients with HCC after radicalhepatectomy was detected. CD4, CD25 and CD127 were selected as Treg cell makers to phenotype cell populations. The expression of FOXp3 mRNA was also analyzed. The migration and proliferation of Treg cells were observed. Interleukin (IL)-4, IL-10, IFN-γ and SDF-1 in cell supernatant were detected. For all tests, functions of Treg cells were evaluated after treatment with APS.</p><p><b>RESULTS</b>APS can inhibit the growth and proliferation of CD4+CD25+Treg cells in vitro in a dose- and time-dependent manner. APS may inhibit CD4+CD25+Treg cells through restoring the cytokine imbalance and reducing the expression of FOXp3 in local HCC microenvironments. SDF-1 played an important role in there recruitment of Treg cells into the tumor microenvironment of HCC. APS might have inhibiting effects on Treg cell migration by blocking SDF-1 or its receptor through the CXCR4/CXCL12 pathway.</p><p><b>CONCLUSIONS</b>The increase in numbers of tumor associated Treg cells might play a role in modulation of the immune response against HCC. APS can restore the cytokine balance in the tumor micro environment and suppress the expression of FOXp3 mRNA to inhibit the immune suppressive effects of Treg cells. The application of APS in the tumor microenvironment might act to enhance the anti-tumor effects of the immunotherapy-based methods, and consequently to increase the survival rate in HCC.</p>

Effects of antiallergic herbal agents on cystic fibrosis transmembrane conductance regulator in nasal mucosal epithelia of allergic rhinitis rabbits / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been found that the expression of cystic fibrosis transmembrane conductance regulator (CFTR) is closely related to allergic rhinitis (AR). In the previous study, we have demonstrated that antiallergic herbal agents (AHA) can obviously inhibit the allergic reaction of AR. The aim of this study was to explore the expression of CFTR and the effects of AHA on CFTR to improve the allergic reaction of AR.</p><p><b>METHODS</b>An animal model of an AR rabbit was established using ovalbumin (OVA). The rhinitis rabbits were randomly assigned to three groups: AHA treating group (AHATG), modeling group (MG) and healthy controlling group (HCG). The expressions of CFTR protein were examined by immunohistochemical method. The mucosal epithelial cells of all the rabbits were primarily cultured with tissue culture method in vitro and treated with or without glibenclamide for 24 hours. The levels of monocyte chemotactic factor-1 (MCP-1) and RANTES protein in supernatants of culture were measured by ELISA, and the expressions of CFTR mRNA were detected by real-time PCR.</p><p><b>RESULTS</b>The expressions of CFTR mRNA and protein greatly increased in mucosal epithelial cells of MG. The protein concentrations of MCP-1, RANTES in culture supernatants of MG were significantly higher than those in the other two groups (P < 0.01), and they reached much higher level than those at the start points in the MG (P < 0.05) and were significantly different compared with those in the AHATG after being cultured for 24 hours (P < 0.01). CFTR mRNA in MG + glibenclamide were much lower than those in MG (P < 0.05). RANTES and CFTR mRNA treated with glibenclamide in AHATG were significantly lower than those in the AHATG (P < 0.01). Minimal changes in the secretions of MCP-1 in the epithelial cells were detected between AHATG and AHATG + glibenclamide (P > 0.05).</p><p><b>CONCLUSIONS</b>AHA can inhibit the secretions of CFTR, RANTES and MCP-1 in mucosal epithelia and improve inflammatory reaction of AR. CFTR may play an important role in the secretion of RANTES and mucosal inflammatory response in AR. Glibenclamide can inhibit the CFTR secretion in mucosal epithelial cells, in particular during AR process. These effects of glibenclamide on secretion of RANTES can be effectively strengthened by AHA.</p>