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The development of medications known as immune checkpoint inhibitors(ICPis) has been a milestone of cancer therapy. However, the increasing use of ICPis in recent years has caused a diverse spectrum of immune-related adverse events, including endocrine glands injury. ICPis-induced endocrinopathies are new challenges brought by advances of medicine as well as become the hot topics in both endocrinology and oncology. It is important that endocrinologists and oncologists should know how to perform proper assessment and clinical management once ICPis-induced endocrinopathies occur. Interdisciplinary collaboration is required to deal with this medical problem in order to improve overall survival and quality of life for patients with various cancer.
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OBJECTIVE: To observe the expression of interleukin(IL)-23 and IL-17 in the liver of mice sensitized by trichloroethylene(TCE), and to explore the role of IL-23 and IL-17 in polyinosinic: polycytidylic acid(Poly I:C) exacerbated TCE-sensitized mice with immune injury of the liver. METHODS: Female specific pathogens free BALB/c mice were randomly divided into control group(n=5), solvent control group(n=5), TCE group(n=20), and TCE+Poly I:C group(n=20). A TCE-sensitized mouse model was established in TCE group and TCE+Poly I:C group. Three hours before the last challenge, mice in TCE+Poly I:C group was intraperitoneally injected with a mass concentration of 0.5 g/L poly I:C, 100 μL per mouse. The two groups of mice were divided into sensitized and non-sensitized subgroups according to the results of skin sensitization. After 48 hours of the final challenge, serum alanine aminotransferase(ALT) was detected by colorimetric method. The histopathological changes of mouse liver were observed, and the expression of IL-23 and IL-17 in liver tissues was detected by immunohistochemistry and Western blotting method. RESULTS: The sensitization rates of TCE and TCE+Poly I:C groups were 35.0%(7/20) and 40.0%(8/20) respectively, with no significantly statistical difference(P>0.05). Pathological examination showed that there was cell edema in some areas of the liver tissues of mice in the TCE-sensitized subgroup, while the TCE+Poly I:C sensitized subgroup showed cell vacuolar degeneration and loose cytoplasm. Serum ALT activity and the expression of IL-23 and IL-17 in liver tissues in the TCE-sensitized subgroup were higher than that in the blank control group, the solvent control group and the TCE non-sensitized subgroup(P<0.05). Serum ALT activity and IL-23 and IL-17 expression in the TCE+Poly I:C sensitized subgroup were higher than that in the TCE-sensitized subgroup(P<0.05). The relative expression of IL-23 and IL-17 protein in liver tissues in TCE-sensitized subgroup was higher than that of the blank control group and the solvent control group(P<0.05), while that in TCE+Poly I:C sensitized subgroup was higher than that of TCE-sensitized subgroup(P<0.05). CONCLUSION: IL-23/IL-17 axis may play an important role in the development of immune injury of liver in the TCE-sensitized mice and Poly I:C exacerbated TCE-sensitized mice.
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Objective@#To investigate the role of lysosome-associated membrane protein type 2A (LAMP-2A) for immune-mediated liver injury of primary biliary cholangitis (PBC).@*Methods@#The association between LAMP-2A expression and PBC was examined by immunohistochemistry and electron microscopy in liver tissue samples from patients with PBC. Furthermore, the immunological damage of LAMP-2A overexpression on mouse liver was observed by adeno-associated virus (AAV) overexpression technique. The expression level of mRNA was analyzed by Student's t-test. The data were graphed and analyzed statistically using graphpad prism 5 (GraphPad Software).A value of p < 0.05 was considered statistically significant.@*Results@#The expression of LAMP-2A in liver tissue of PBC patients was increased, and the autophagosome formation was observed in hepatocytes. C57BL/6 mice were injected into the caudal vein with LAMP-2A AAV for 6 weeks. The formation of autophagosomes in mouse hepatocytes was increased significantly. The expression of related molecules was abnormal; simultaneously, the degree of lymphocyte infiltration in the liver tissue of mice was significantly higher than the control group.@*Conclusion@#An overexpression of LAMP-2A in the liver of patients with PBC may induce and/or promote the hepatic inflammatory response, especially the portal inflammatory infiltrate.
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Immune response after blood transfusion is closely related to prognosis of the patients receiving blood productions. Thus, the safety and effectiveness are paid increasing attention.This article reviews immunological consequence and clinical manifesta-tions and response strategies after transfusion, which aims to provide reference for clinical transfusion decisions.
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Objective To investigate the immune injury in genital tract of BALB/c mice induced by plasmid protein pORF5 of Chlamydia trachomatis and its possible mechanism.Methods GST(glutathione-S-transferases)-pORF5 fusion protein was expressed and digested with PreScission Protease to obtain the target protein without GST tag.After further purification and endotoxin removal,pORF5 protein was injected into the posterior fornix of BALB/c mice on day 1,3 and 6,while the control groups were injected with PBS or GST protein respectively,and then all the mice were sacrificed on day 7 to evaluate genital tract gross pathology and histopathological characterization.The levels of TNF-α,IL-1β and IL-6 in serum,splenocytes culture supernatant and vaginal douche were detected by ELISA.Results Mice in pORF5 group developed different degrees of swelling in isthmic portion and ampulla of uterine tube,connective tissue adhesion and hydrosalpinx in the genital tract tissues,while the PBS group and the GST group did not show any obvious change.The inflammatory score showed that the genital tract pathology in pORF5 group was much more severe than PBS and GST control groups (P＜0.O1).The levels of TNF-α,IL-1β and IL-6 in vaginal douche and splenocytes culture supernatants in pORF5 group were obviously higher than those of PBS and GST groups (P＜0.05).The levels of TNF-α and IL-1β in serum were also higher than those of GST and PBS groups (P＜0.01).Conclusion pORF5 plasmid protein could induce pathological immune response in the genital tract of BALB/c mice,which may be associated with the increase of the production of the inflammatory cytokines TNF-α,IL-1β and IL-6 in BALB/c mice.
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Henoch-Schonlein purpura(HSP) is one of the most common blood capillary allergic disorder in children, and its pathogenesis has not been well explained. The studies show that the main mechanism of HSP is the abnormality of humoral immunity, and the role of IgA is emphaszed. Meanwhile, many agents such as changes in T cell function,participation of cytokine and mediators of intlammation, suscepti-bility gene and other factors also play an important role in the incidence of HSP. The pathogenesis of HSP can be better understood through extensive analysis of the immunology factors,genetic factors,and so on.
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0.05). But according to the data, IL-8 in Qingqinye low dosage group was lower than model group, positive medicine group, Qingqinye high dosage group and Qingqinye middle dosage group. TNF-? in Qingqinye group was lower than model group and positive medicine group, especially in Qingqinye middle dosage group. Pathological section with articular cavity and surrounding tissues were better in positive medicine group and Qingqinye group. Conclusion Qingqinye has a certain effect for repairing joint immune pathological injury in hyperuricemia model rats.