ABSTRACT
Objective@#To explore effects of histone deacetylase inhibitor Belinostat on the immunologic function of dendritic cells (DC) and its possible mechanism.@*Methods@#Cultured mouse bone marrow-derived DC from C57BL/6 mouse in vitro. The experiments were divided into 0, 50, 100 nmol/L Belinostat + immature DC (imDC) group, and 0, 50, 100 nmol/L Belinostat mature DC (mDC). The changes of the ultrastructure of DC were observed by transmission electron microscope (TEM). Immunophenotype and CCR7 expression rate were detected by FCM, and the migration rate was observed by chemotaxis assay. The proliferation of lymphocytes stimulated by different DC was detected by mixed lymphocyte culture reaction. The cytokines in the culture supernatant, including TNF-α, IL-12 and IL-10, were examined by ELISA. RQ-PCR was used to examine the relative expression of mRNA in RelB.@*Results@#Successful cultured and identified the qualified imDC and mDC. Belinostat decreased the expression of CCR7 on imDC [(25.82±7.25)% vs (50.44±5.61)% and (18.71±2.00)% vs (50.44±5.61)%], meanwhile increased the rate on mDC [(71.14±1.96)% vs (64.90±1.47)%]. Chemotaxis assay showed that the migration rate of Belinostat+imDC and Belinostat+mDC group were both decreased, but the difference in imDC was not significant. T lymphocyte proliferation rate stimulated by 100 nmol/L Belinostat+imDC group was lower than imDC group in condition irritation cell∶reaction cell=1∶2 [(227.09±13.49)% vs (309.49±53.69)%]. Belinostat significantly suppressed the secretion of cytokines TNF-α, IL-12 and IL-10 (all P<0.01). The relative expression of mRNA in RelB was slightly decreased in Belinostat+imDC and Belinostat+mDC group (all P<0.05).@*Conclusion@#Belinostat could effectly suppress DC maturation and regulate immune tolerance of DC, which may be due to the down-regulation of mRNA level of RelB in DC.
ABSTRACT
BACKGROUND: Bone marrow necrosis has unspecific clinical features, which is often misdiagnosed or missed due to a lack of the knowledge of the disease. OBJECTIVE: To improve the awareness and vigilance to bone marrow necrosis, and to further explore the clinical manifestations, hematological characteristics, pathogenesis and treatment of bone marrow necrosis. METHODS: The bone marrow necrosis, hematologic neoplasms, solid tumor, bone marrow puncture, bone marrow pathology in Chinese and English served as the search terms to search articles related to bone marrow necrosis in PubMed and Wanfang databases, published from 1941 to 2016. Totally 43 articles were selected for review. RESULTS AND CONCLUSION: Bone marrow necrosis is a rare complication caused by various diseases, clinically characterized by bone pain, fever, anemia, and nucleated red cells and immature neutrophilic leukocytes in the blood smear. Bone marrow aspiration and/or bone marrow biopsy show(s) necrotic features. Its pathogenesis is complex, and it is still poorly understood and needs further research. There is no good treatment for bone marrow necrosis, and the prognosis is poor. Early correct diagnosis and etiological treatment are crucial for the prognosis of bone marrow necrosis.With the improvement of disease awareness, bone marrow cytology, genetics, MRI and hematopoietic stem cell transplantation, bone marrow necrosis is expected to get a better prognosis.