共查询到20条相似文献,搜索用时 15 毫秒
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Anoxia-Induced Up-Regulation of Interleukin-8 in Human Malignant Melanoma : A Potential Mechanism for High Tumor Aggressiveness 总被引:8,自引:0,他引:8
Manfred Kunz Anke Hartmann Egbert Flory Atiye Toksoy Dirk Koczan Hans-Jürgen Thiesen Nafoumi Mukaida Manfred Neumann Ulf Rüdiger Rapp Eva-Bettina Brcker Reinhard Gillitzer 《The American journal of pathology》1999,155(3):753-763
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Recent studies indicate that nitric oxide (NO) or related compounds may regulate the production of interleukin (IL)-8, a potent proinflammatory chemokine. Here we report that peroxynitrite (ONOO(-)) formed by a reaction of NO with superoxide mediates IL-8 gene expression and IL-8 production in IL-1beta- and TNF-alpha-stimulated human leukocytes in whole blood. The NO synthase inhibitors aminoguanidine and N(G)-nitro-L-arginine methyl ester blocked nuclear accumulation of activator protein-1 (AP-1) and nuclear factor (NF)-kappaB in both polymorphonuclear (PMN) and mononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8 release by approximately 90% in response to IL-1beta and TNF-alpha. Enhanced ONOO(-) formation was detected in granulocytes, monocytes, and lymphocytes after challenge with IL-1beta or TNF-alpha. The addition of ONOO(-) (0.2-80 microM) to whole blood increased nuclear accumulation of AP-1 and NF-kappaB in PMN and mononuclear leukocytes and augmented IL-8 mRNA expression and IL-8 production in a concentration-dependent fashion. Pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, attenuated approximately 70% of IL-8 release evoked by IL-1beta, TNF-alpha, or ONOO(-). These results indicate that ONOO(-) formation may underlie the action of cytokines towards IL-8 gene expression in human leukocytes. 相似文献
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Prabhudas S Patel Michelle L Varney Bhavana J Dave Rakesh K Singh 《Journal of interferon & cytokine research》2002,22(4):427-435
In the present study, we demonstrate that upregulation of interleukin-1beta(IL-1beta)-mediated and tumor necrosis factor-alpha (TNF-alpha)-mediated IL-8 expression in human malignant melanoma cells is modulated by the activation of nuclear factor-kappaB (NF-kappaB). Addition of capsaicin (8-methyl-N-vanillyl-6-nonenamide), a known inhibitor of NF-kappaB, resulted in the inhibition of constitutive as well as IL-1beta-induced and TNF-alpha-induced IL-8 expression in melanoma cells. The inhibition of IL-8 expression was dependent on the concentration of capsaicin and duration of treatment. Further, electrophoretic mobility shift assay (EMSA) of nuclear extracts from melanoma cells showed a constitutive activation of NF-kappaB and activated protein 1 (AP-1), which was upregulated following treatment with IL-1beta. Treatment of melanoma cells with capsaicin inhibited activation of constitutive and IL-1beta-induced NF-kappaB, but not AP-1, leading to inhibition of IL-8 expression. Further, downregulation of IL-8 expression in capsaicin-treated melanoma cells resulted in inhibition of in vitro cell proliferation. These results demonstrate that constitutive and induced NF-kappaB activation regulates IL-8 expression in melanoma cells. Downregulation of constitutive and induced NF-kappaB activation in malignant melanoma cells leads to inhibition of IL-8 production and in vitro cell proliferation. 相似文献
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Lorentz A Klopp I Gebhardt T Manns MP Bischoff SC 《The Journal of allergy and clinical immunology》2003,111(5):1062-1068
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Yoshihide Shimojo Miho Akimoto Tsunehiro Hisanaga Tsuneo Tanaka Yoshitsugu Tajima Yoshio Honma Keizo Takenaga 《Clinical & experimental metastasis》2013,30(2):143-154
Hypoxia has been shown to promote metastasis of cancer cells through induction of epithelial-mesenchymal transition (EMT). It is also known to cause generation of reactive oxygen species (ROS). We investigated here the role of ROS in hypoxia-induced EMT and whether attenuation of ROS by antioxidants suppresses hypoxia-induced EMT and metastasis of human pancreatic cancer cells in a xenograft nude mouse model. PANC-1 and MiaPaCa-2 cells exposed to hypoxia (1 % O2) showed increased ROS generation and characteristic changes of EMT such as morphological changes, enhanced invasiveness, and upregulation of EMT regulators, SLUG, SNAI1 and TWIST. The antioxidants N-acetylcysteine (NAC) and ebselen significantly suppressed EMT and the expression of EMT regulators during hypoxia. NAC abrogated activation of HIF-1α and NF-κB, both of which were found to play an active role in hypoxia-induced EMT. Administration of NAC to nude mice with orthotopic tumors suppressed the expression of EMT regulators in hypoxic areas and significantly inhibited hepatic metastasis. Together, the present findings demonstrate that attenuation of ROS by antioxidants suppresses hypoxia-induced EMT and metastatic phenotype, suggesting that antioxidants may be of therapeutic value in treating pancreatic cancers. 相似文献
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Enterohemorrhagic Escherichia coli infection induces interleukin-8 production via activation of mitogen-activated protein kinases and the transcription factors NF-kappaB and AP-1 in T84 cells
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Dahan S Busuttil V Imbert V Peyron JF Rampal P Czerucka D 《Infection and immunity》2002,70(5):2304-2310
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