Type I Interferons and Interferon Regulatory Factors Regulate TNF-Related Apoptosis-Inducing Ligand (TRAIL) in HIV-1-Infected Macrophages

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family that participates in HIV-1 pathogenesis through the depletion of CD4+ T cells. TRAIL is expressed on the cell membrane of peripheral immune cells and can be cleaved into a soluble, secreted form. The regulation of TRAIL in macrophages during HIV-1 infection is not completely understood. In this study, we investigated the mechanism(s) of TRAIL expression in HIV-1-infected macrophages, an important cell type in HIV-1 pathogenesis. A human monocyte-derived macrophage (MDM) culture system was infected with macrophage-tropic HIV-1ADA, HIV-1JR-FL, or HIV-1BAL strains. TRAIL, predominantly the membrane-bound form, increased following HIV-1 infection. We found that HIV-1 infection also induced interferon regulatory factor (IRF)-1, IRF-7 gene expression and signal transducers and activators of transcription 1 (STAT1) activation. Small interfering RNA knockdown of IRF-1 or IRF-7, but not IRF-3, reduced STAT1 activation and TRAIL expression. Furthermore, the upregulation of IRF-1, IRF-7, TRAIL, and the activation of STAT1 by HIV-1 infection was reduced by the treatment of type I interferon (IFN)-neutralizing antibodies. In addition, inhibition of STAT1 by fludarabine abolished IRF-1, IRF-7, and TRAIL upregulation. We conclude that IRF-1, IRF-7, type I IFNs, and STAT1 form a signaling feedback loop that is critical in regulating TRAIL expression in HIV-1-infected macrophages

Unmet supportive care needs among colorectal cancer patients in Hong Kong

Conference Theme: Medical Leadership and Management - Global Outlook and Local LandscapeAbstract & poster presentatio

Prediction of persistent carbohydrate intolerance in patients with gestational diabetes

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Review of experience over four decades in the management of carotid body tumours

Objective: To review the experience of the management of carotid body tumours in a major vascular centre in mainland China. Patients and methods: This was a retrospective review of 52 cases of carotid body tumour. There were 24 male and 28 female patients with an age range of 18-67 years; and 23 right-sided, 24 left-sided and five bilateral lesions. The modality of preoperative imaging was as follows: duplex scan and computed tomography in 40 cases, magnetic resonance imaging in 10 cases, carotid artery angiogram in 32 cases with selective embolization of the feeding vessel in 19. Operative treatment was carried out for 55 lesions and was summarized as follows: simple tumour excision for 44 lesions and en bloc tumour excision together with carotid bifurcation for 11 lesions; ICA reconstruction with interposition graft in three cases; and external to ICA anastomosis in two cases. Results: There were no operative mortalities. Postoperative complications included two ischaemic strokes, one case of vagus nerve damage and one case of hypoglossal nerve damage. Conclusion: Carotid body tumour is a rare neoplasm. Its special anatomical position imposes great difficulty during surgery. Adequate preoperative preparation and embolization of feeding arteries could reduce operative blood loss, improve tumour excision and preserve the ICA flow.link_to_subscribed_fulltex