1.Inhibitory effect of Hsp70 on angiotensin II-induced vascular smooth muscle cell hypertrophy.
Ying ZHENG ; Chang Nim IM ; Jeong Sun SEO
Experimental & Molecular Medicine 2006;38(5):509-518
Angiotensin II (Ang II), which is an important mediator of both vascular responsiveness and growth, has been shown to induce vascular smooth muscle cell (VSMC) hypertrophy via the activation of a complex series of intracellular signaling events. Heat shock protein 70 (Hsp70) has recently been shown to protect against Ang II-induced hypertension. In this study, we tested the hypothesis that Hsp70 can protect VSMC from Ang II-induced hypertrophy. We treated VSMCs with Ang II to induce hypertrophy and to activate MAPK signaling pathway. We observed that the augmentation of Hsp70 expression inhibited Ang II-stimulated VSMC hypertrophy. This inhibitory effect of Hsp70 appears to be partly due to extracellular signal-regulated kinase (ERK1/2) inactivation, which in turn, may possibly result from the accumulation of MAP kinase phosphatase-1 (MKP-1).
Rats, Sprague-Dawley
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Rats
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RNA, Small Interfering/pharmacology
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Protein-Tyrosine-Phosphatase/metabolism/physiology
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Phosphoprotein Phosphatase/metabolism/physiology
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Muscle, Smooth, Vascular/*cytology/*drug effects
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Mitogen-Activated Protein Kinase 3/antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1/antagonists & inhibitors
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Male
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MAP Kinase Kinase 2/metabolism
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MAP Kinase Kinase 1/metabolism
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Immediate-Early Proteins/metabolism/physiology
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Hypertrophy
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HSP70 Heat-Shock Proteins/antagonists & inhibitors/*pharmacology
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Flavonoids/pharmacology
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Enzyme Stability/drug effects
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Cells, Cultured
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Cell Cycle Proteins/metabolism/physiology
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Aorta/drug effects/pathology
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Animals
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Angiotensin II/*pharmacology
2.Iron chelator inducesMIP-3alpha/CCL20 in human intestinal epithelial cells: implication for triggeringmucosal adaptive immunity.
Hyun Ju LEE ; Suck Chei CHOI ; Eun Young CHOI ; Moo Hyung LEE ; Geom Seog SEO ; Eun Cheol KIM ; Bong Joon YANG ; Myeung Su LEE ; Yong Il SHIN ; Kie In PARK ; Chang Duk JUN
Experimental & Molecular Medicine 2005;37(4):297-310
A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs). Microarray-based gene expression profiling revealed that iron chelator also induces macrophage inflammatory protein 3 alpha (MIP-3alpha)/ CC chemokine-ligand 20 (CCL20). As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as recombinant human CCL20 at equivalent concentrations to attract CCR6+ cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human PBMCs and in THP-1 cells, but not in human umbilical vein endothelial cells. Interestingly, unlike other proinflammatory cytokines, such as TNF-alpha and IL-1beta, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-alpha-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.
Calcium/metabolism
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Cell Movement/drug effects
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Chemokines, CC/genetics/*metabolism
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Deferoxamine/*pharmacology
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Egtazic Acid/analogs & derivatives/pharmacology
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HT29 Cells
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Humans
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Immunity, Mucosal/*drug effects
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Intestinal Mucosa/*drug effects/immunology/metabolism
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Iron Chelating Agents/*pharmacology
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Macrophage Inflammatory Proteins/genetics/*metabolism
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NF-kappa B/metabolism
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Phosphoprotein Phosphatase/physiology
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Protein Transport/drug effects
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Protein-Serine-Threonine Kinases/physiology
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RNA, Messenger/genetics/metabolism
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Receptors, Chemokine/metabolism
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Research Support, Non-U.S. Gov't