CX3C-chemokine receptor 1 modulates cognitive dysfunction induced by sleep deprivation / 中华医学杂志(英文版)

BACKGROUND@#Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD.@*METHODS@#Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes.@*RESULTS@#CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted.@*CONCLUSIONS@#These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

Interleukin-17 Indirectly Promotes M2 Macrophage Differentiation through Stimulation of COX-2/PGE2 Pathway in the Cancer Cells / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Interleukin-17 (IL-17) is a proinflammatory cytokine that plays important roles in inflammation, autoimmunity, and cancer. The purpose of this study was to determine if IL-17 indirectly regulates macrophage differentiation through up-regulation of cyclooxygenase-2 (COX-2) expression in the cancer cell lines. MATERIALS AND METHODS: Human cervical cancer HeLa, human lung cancer A549, and mouse prostate cancer Myc-CaP/CR cell lines were treated with recombinant IL-17; Western blot analysis, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction analysis were utilized to examine the cellular responses. RESULTS: IL-17 up-regulated expression of COX-2 mRNA and protein in HeLa, A549, and Myc-CaP/CR cell lines. IL-17's effects were mediated through nuclear factor-kappaB and ERK1/2 signaling pathways as the inhibitors of these pathways could inhibit IL-17-induced COX-2 expression. The conditional medium obtained from the cancer cells contained prostaglandin E2, the levels of which were increased by IL-17 treatment. When treated with the conditional medium, particularly with the IL-17-induced conditional medium, mouse RAW264.7 macrophages and human THP-1 monocytes expressed higher levels of IL-10 (a marker of M2 macrophages) than inducible nitric oxide synthase or tumor necrosis factor alpha (markers of M1 macrophages). In contrast, when RAW264.7 and THP-1 cells were treated directly with IL-17, expression of these marker genes was not markedly changed. CONCLUSION: The results of this study suggest that IL-17 indirectly promotes M2 macrophage differentiation through stimulation of the COX-2/PGE2 pathway in the cancer cells, thus IL-17 plays an indirect role in regulating the tumor immune microenvironment.

THE EFFECTS OF EXPERIMENTAL VARICOCELE ON THE MICROSTRUCTURE AND ULTRASTRUCTURE OF THE EPIDIDYMIS IN ADOLESCENT RATS / 解剖学报

Objective To study the microstructural and ultrastructural changes of the epididymis of experimental varicocele in adolescent rats and it's role in infertility resulting from varicocele. Methods A varicocele model was performed in adolescent Sprague Dawley rats by partially ligating the left renal vein,the different segments of the epididymides of the rats were prepared for light and electron microscopy,the microstructure and ultrastructure of the epididymis were studied. Results There were lesions of different degree and segment specific changes in the epididymis with varicocele.Light microscopically,the main changes were interstitial vascular hyperemia,lymphocytes infiltration,sperm granuloma developed in the interstitial;The structure of the columnar epithelia was anomalies,epithelial cells degeneration,even the vacuoles appeared in the epithelial cells.The number of halo and clear cells increased.Inside the cavity of the duct,there were shedding cells,macrophage,deformed sperms and residual bodies.Electron microscopically,numerous large lysosomes,the residual bodies,the defected main cellular organelles(e.g. the endoplasmic reticulum,the mitochondrion and the Golgi complex etc.)and even large clear vacuoles were presented in the cytoplasm of principal cells.Clear cells were filled with lysosomes that made them frequently bulging into the lumen.The microvilli of the columnar epithelia were sparse and showed local defects.The thickness of the basal membrane increased.Conclusion\ The experimental varicocele in adolescent rats lead to microstructure and ultrastructure lesions in the epididymis,which may be another important reason of infertility resulting from varicocele.\;[