Modulation of Wnt/ß-catenin signaling in IL-17A-mediated macrophage polarization of RAW264. 7 cells

Macrophages play pivotal roles in host defense and immune homeostasis, which have two major functional polarization states, the classically activated M1 and the alternatively activated M2. Interleukin (IL)-17A is an immune modulator able to shape macrophage phenotypes. Wnt/β-catenin is a developmental signaling pathway that plays crucial roles in morphogenesis and tissue homeostasis, which has also been recently demonstrated playing roles in immune regulation. A growing amount of evidence suggests that both Wnt and IL-17A signaling are involved in macrophage polarization. However, their interaction in macrophage polarization remains elusive. The aim of present study was to explore impacts of Wnt/β-catenin on IL-17A-mediated macrophage M1/M2 polarization in murine monocyte/macrophage-like cell line RAW264.7. Results revealed that IL-17A activated Wnt/β-catenin signaling and induced macrophage M1 polarization, but inhibited M2 polarization. In contrast, the activation of Wnt/β-catenin signaling led to the inhibition of M1 macrophage polarization but the promotion of M2 polarization. Importantly, the activation of Wnt/β-catenin also showed abilities to inhibit the IL-17A-induced M1 macrophage polarization while diminishing the IL-17A-inhibited M2 polarization. Molecular analysis further uncovered that the JAK/STAT signaling pathway was involved in the interaction of Wnt/β-catenin and IL-17A in the modulation of macrophage polarization. These results suggested that the Wnt/β-catenin signaling modulated IL-17A-altered macrophage polarization in part by regulating the JAK/STAT signaling pathway. This study thus revealed a novel function of Wnt/β-catenin signaling in regulating IL-17A-altered macrophage polarization.

Influence of alcohol consumption on liver function and rebleeding in alcoholic cirrhotic patients with esophageal and gastric varices / 临床肝胆病杂志

@#ObjectiveTo investigate the influence of alcohol consumption on liver function and prognosis in alcoholic cirrhotic patients. MethodsA total of 211 alcoholic cirrhotic patients with gastroesophageal variceal bleeding who underwent endoscopic treatment in Beijing Ditan Hospital, Capital Medical University, from September to December, 2018 were enrolled, and among these patients, there were 208 male and 3 female patients, with a mean follow-up time of 45 months (range 2-110 months). The association of alcohol consumption with liver parameters was analyzed. According to the presence or absence of gastroesophageal variceal rebleeding, the patients were divided into early rebleeding group, delayed rebleeding group, and non-rebleeding group, and the three groups were compared in terms of liver parameters and alcohol consumption. The t-test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The Spearman rank correlation test was used for correlation analysis. ResultsDuration of drinking was correlated with creatinine (r=0.142, P=0.039) and direct bilirubin (DBil) (r=-0.137, P=0.047), and daily alcohol consumption was correlated with DBil (r=0.144, P=0.037) and prealbumin (r=-0.190, P=0.009), while there was no correlation between total alcohol consumption and indicators for liver injury. There were significant differences between the early rebleeding group and the delayed rebleeding group in white blood cell count (WBC) (t=-2.355, P=0.020), neutrophils (t′=-2.602, P=0.010), hemoglobin (t=2.247, P=0.026), mean corpuscular volume (t=-2.073, P=0.040), alanine aminotransferase (Z=-1.985, P=0047), international normalized ratio (Z=-2.397, P=0.017), spleen thickness (Z=-2.542, P=0.011), Child-Pugh score (t′=-2.364, P=0.020), and Child-Pugh grade (Z=-2.485, P=0.013). The non-rebleeding group had significantly lower WBC (Z=-2.276, P=0.017) and neutrophils (Z=-2.375, P=0.018) than the rebleeding group, and the early and delayed rebleeding groups had a significantly shorter duration of drinking than the non-rebleeding group (Z=-2.522, P=0.012). The logistic regression analysis showed that neutrophils was a risk factor for variceal rebleeding (odds ratio=1.152, 95% confidence interval: 1.017-1.300, P=0026). ConclusionNo dose-response relationship is found between alcohol consumption and liver injury in this study, and alcohol consumption may not have a marked effect on variceal rebleeding.

A novel DNA vaccine constructed by heat shock protein 70 and melanoma antigen-encoding gene 3 against tumorigenesis.

Melanoma antigen-encoding gene 3 (MAGE-3) is an ideal candidate for a tumor vaccine although its potency need to be increased. Heat shock proteins (HSPs) represents a potential approach for increasing the potency of DNA vaccines. In the present study, a fusion DNA vaccine composed of Mycobacterium tuberculosis HSP70 and MAGE-3 was constructed and used to immunize C57BL/6 mice against B16 or B16-MAGE-3 tumor cells. The results show that the HSP70-MAGE-3 fusion DNA vaccine enhanced the frequency of MAGE-3-specific cytotoxic T-cells as compared to the MAGE-3 DNA vaccine or the HSP70/MAGE-3 cocktail DNA vaccine (P<0.05). In conclusion, the results indicate that the HSP70-MAGE-3 fusion DNA vaccine can strongly activate MAGE-3 specific cellular immunological reactions and thus significantly inhibit the growth of B16-MAGE-3 tumors, improving the survival of tumor-bearing mice, and the HSP70-MAGE-3 fusion DNA vaccine has a significant therapeutic effect on the tumors that express MAGE-3 antigens.