Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins, such as tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113）, which play major role in the neuronal death. It h...Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins, such as tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113）, which play major role in the neuronal death. It has been shown that different HIV-1 variants have varying abilities to elicit secretion of TNF-a by peripheral blood mononuclear cell （PBMC）; however, whether the difference of gp120 gene could affect the secretion of TNF-a and IL-113 by glial cells is unknown. The aim of this study was to explore the association between gene diversity and induction of neurotoxic cytokines. Methods In this study, we constructed retroviral vectors MSCV-IRES-GFP/gp120 using HIV-1 gp120 genes isolated from four different tissues of one patient who died of AIDS dementia complex （ADC）. Recombinant retroviruses produced by cotransfection of MSCV-IRES-GFP/gp120, pCMV-VSV-G and pUMVC into 293T cells were collected and added into U87 glial cells. Concentrations of TNF-α and IL-1β secreted by transduced U87 cells were assayed with ELISA separately. Results The four HIV-1 gp120 were in the different branch of the neighbor-joining tree. Compared to the pMIG retrovirus （gp120-negative） or U87 cells, all the gp120-positive recombinant retroviruses induced more TNF-a （P 〈0.01） and IL-113 （P 〈0.01）. In addition, compared with the L/MIG retrovirus, all the three brain gp120-positive recombinant retroviruses induced less TNF-α （P 〈0.01） and IL-1β （P 〈0.01）. Conclusions HIV-1 gp120 could induce U87 cells secret more TNF-α and IL-1β again. The more important is that difference of HIV-1 gp120, especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1 β, which might supply a novel idea helping understand the pathogenesis of ADC.展开更多
Background The precise mechanisms responsible for the development and growth of intracranial arteriovenous malformations （AVMs） remain unclear. Osteopontin （OPN） is a phosphorylated glycoprotein with diverse funct...Background The precise mechanisms responsible for the development and growth of intracranial arteriovenous malformations （AVMs） remain unclear. Osteopontin （OPN） is a phosphorylated glycoprotein with diverse functions. This study aimed to analyze the expression of OPN in human brain AVMs. Methods The AVM nidus was surgically obtained from patients with AVM, whereas control brain artery specimens were surgically obtained from patients with epilepsy. Reverse transcription-polymerase chain reaction （RT-PCR） was used to examine the expression of OPN mRNA in biopsy specimens. OPN protein expression was localized by immunohistochemistry. The statistical differences between different groups were assessed by two-way analysis of variance （ANOVA）. Results We analyzed 36 brain AVM specimens and 8 control brain artery specimens. Eleven patients with brain AVM received embolization treatment, and five underwent gamma knife radiotherapy before resection. Nineteen patients with brain AVM had a history of hemorrhage from AVMs. The expression of OPN mRNA was significantly higher in AVMs than that in the control specimens （25.76＋2.71 vs. 21.46＋2.01, P 〈0.01）. There was no statistically significant difference in the extent of OPN mRNA expression between the AVM group with and that without history of hemorrhage （26.13＋2.45 vs. 25.34＋2.99） or gamma knife radiotherapy （24.39：1：2.10 vs. 24.53＋1.85）, However, the difference between the AVM group with and that without embolization treatment history was statistically significant （24.39＋2.10 vs. 28.80＋1.13, P 〈0.01）. In the group with gamma knife radiotherapy history, OPN expression was found in arteries with early-stage radio-effect. Conclusions OPN may contribute to the vascular instability of brain AVMs. It may play an important role in the pathophysiological process related to embolization treatment.展开更多
文摘Background HIV-1 infected and immune-activated macrophages and microglia secrete neurotoxins, such as tumor necrosis factor-a （TNF-a） and interleukin-113 （IL-113）, which play major role in the neuronal death. It has been shown that different HIV-1 variants have varying abilities to elicit secretion of TNF-a by peripheral blood mononuclear cell （PBMC）; however, whether the difference of gp120 gene could affect the secretion of TNF-a and IL-113 by glial cells is unknown. The aim of this study was to explore the association between gene diversity and induction of neurotoxic cytokines. Methods In this study, we constructed retroviral vectors MSCV-IRES-GFP/gp120 using HIV-1 gp120 genes isolated from four different tissues of one patient who died of AIDS dementia complex （ADC）. Recombinant retroviruses produced by cotransfection of MSCV-IRES-GFP/gp120, pCMV-VSV-G and pUMVC into 293T cells were collected and added into U87 glial cells. Concentrations of TNF-α and IL-1β secreted by transduced U87 cells were assayed with ELISA separately. Results The four HIV-1 gp120 were in the different branch of the neighbor-joining tree. Compared to the pMIG retrovirus （gp120-negative） or U87 cells, all the gp120-positive recombinant retroviruses induced more TNF-a （P 〈0.01） and IL-113 （P 〈0.01）. In addition, compared with the L/MIG retrovirus, all the three brain gp120-positive recombinant retroviruses induced less TNF-α （P 〈0.01） and IL-1β （P 〈0.01）. Conclusions HIV-1 gp120 could induce U87 cells secret more TNF-α and IL-1β again. The more important is that difference of HIV-1 gp120, especially cell-tropism may account for the different ability in eliciting secretion of TNF-α and IL-1 β, which might supply a novel idea helping understand the pathogenesis of ADC.
基金This study was supported by a grant of the National Natural Science Foundation of China （No. 81000489）.
文摘Background The precise mechanisms responsible for the development and growth of intracranial arteriovenous malformations （AVMs） remain unclear. Osteopontin （OPN） is a phosphorylated glycoprotein with diverse functions. This study aimed to analyze the expression of OPN in human brain AVMs. Methods The AVM nidus was surgically obtained from patients with AVM, whereas control brain artery specimens were surgically obtained from patients with epilepsy. Reverse transcription-polymerase chain reaction （RT-PCR） was used to examine the expression of OPN mRNA in biopsy specimens. OPN protein expression was localized by immunohistochemistry. The statistical differences between different groups were assessed by two-way analysis of variance （ANOVA）. Results We analyzed 36 brain AVM specimens and 8 control brain artery specimens. Eleven patients with brain AVM received embolization treatment, and five underwent gamma knife radiotherapy before resection. Nineteen patients with brain AVM had a history of hemorrhage from AVMs. The expression of OPN mRNA was significantly higher in AVMs than that in the control specimens （25.76＋2.71 vs. 21.46＋2.01, P 〈0.01）. There was no statistically significant difference in the extent of OPN mRNA expression between the AVM group with and that without history of hemorrhage （26.13＋2.45 vs. 25.34＋2.99） or gamma knife radiotherapy （24.39：1：2.10 vs. 24.53＋1.85）, However, the difference between the AVM group with and that without embolization treatment history was statistically significant （24.39＋2.10 vs. 28.80＋1.13, P 〈0.01）. In the group with gamma knife radiotherapy history, OPN expression was found in arteries with early-stage radio-effect. Conclusions OPN may contribute to the vascular instability of brain AVMs. It may play an important role in the pathophysiological process related to embolization treatment.
