ABSTRACT
With the maturity of surgical techniques, the success rate of liver transplantation has been gradually increased. However, the establishment of long-term immune tolerance after operation still faces multiple challenges. Kupffer cells are tissue-resident macrophages, which could reside in the liver and polarize into different directions following liver transplantation, forming M1 Kupffer cells and M2 Kupffer cells. M1 Kupffer cells have pro-inflammatory function, whereas M2 Kupffer cells possess immunoregulatory function. It contributes to the establishment of immune tolerance by inhibiting the quantity and function of M1 Kupffer cells, or enhancing the quantity and function of M2 Kupffer cells. The polarization of Kupffer cells is regulated by many cytokines and signals, which provides an opportunity for therapies to establish immune tolerance of liver transplantation by interfering Kupffer polarization. In this article, the relationship between Kupffer cell polarization and immune tolerance of liver transplantation, and the mechanism of Kupffer cell polarization were reviewed, aiming to provide reference for establishing immune tolerance of liver transplantation.
ABSTRACT
Pancreatic cancer is highly malignant, and surgical resection is the only cure method at present. In recent years, neoadjuvant therapy has enabled some patients to be successfully downgraded with surgical treatment, which increased the R0 surgical resection rate and prolonged the survival time of patients, has become an important part in the treatment of pancreatic cancer. However, the applicability and standardization of neoadjuvant therapy for pancreatic cancer still need more advanced evidence. This article reviews whether neoadjuvant therapy should be used for resectable pancreatic cancer, the choice of neoadjuvant chemotherapy, and the progress, advantages and disadvantages of neoadjuvant chemoradiotherapy.
ABSTRACT
Objective To isolate and culture rats liver KCS ,and to explore the effect of IRE1-XBP1 pathway on regulation of polarization in activated Kupffer cells (KCs) .Methods (1)Rat KCs were isolated by Ⅳ type collagenase digestion and gradient cen-trifugation methods .(2)KCs were transfected and randomly divided into four groups :XBP1-shRNA group ,Ctrl-shRNA group , AdV-XBP1 group and Ctrl-AdV group .(3)The transfection level of KCs XBP1 ,IL-6 ,IFN-γ ,TNF-α and IL-17 were detected by RT-PCR ;the protein expression level of JAK1 ,JAK2 ,STAT1 and STAT3 were evaluated by Western blot .(4)The changes of KCs expression type in each group were detected by flow cytometry (FCM ) and the laser confocal .(5)T cells derived from rat spleen cells were co-cultured within the 4 groups of KCs mentioned above ;T cells proliferation was measured by Brdu labeling assay .(6)T cells apoptosis was determined by Annexin V /PI FCM analysis .(7)The density of IL-6 ,IFN-γ ,TNF-α ,IL-17 and IL-10 in the su-pernatant of co culture was assessed by ELISA .Results (1)The mRNA and protein level of XBP1 were measured by RT-PCR and western blot ,those in XBP1-shRNA group were significantly reduced compared with those in the other three groups ,while in AdV-XBP1 groups ,results demonstrated entirely the opposite tendency (P< 0 .05) .(2)The expression of marker molecules on the sur-face of KCs such as M HC Ⅱ ,CD86 and CD40 in XBP1-shRNA group were significantly lower (P< 0 .05) ,but CD204 and CD206 expression were much higher compared with the other three (P< 0 .05) .However the expression tendency of these surface markers were shown the opposite results in AdV-XBP1 group (P < 0 .05) .(3)Western blot revealed the XBP1-shRNA could statistically suppress the protein levels and phosphorylation of JAK 1 ,JAK2 ,STAT1 and STAT3 ,which involved in the pro inflammatory cyto-kines regulation and KCs polarization (P< 0 .05) .But in AdV-XBP1 group ,these protein and its phosphorylation were markedly promoted (P< 0 .05) .ELISA results collaborated with Western blot .(4)3 d after co cultured with KCs transfected with XBP1-shR-NA ,the levels of T lymphocyte proliferation and pro inflammatory cytokines secretion were significantly reduced ,but the levels of T lymphocyte apoptosis and anti inflammatory cytokines secretion were remarkably enhanced (P< 0 .05) .Conclusion Blockage of IRE1-XBP1 activation could alter the phenotype of active KCs to M 2 like type and attenuated the capacity of antigen present of KCs ,while up regulated the expression of IRE1-XBP1 pathway could change the phenotype of KCs to M 1 type plus the promotion of antigen present capacity .