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10.1371/journal.pone.0102967 http://scihub22266oqcxt.onion/10.1371/journal.pone.0102967 25051011!4106849!25051011     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       PLoS+One 2014 ; 9 (7): e102967 Nephropedia Template TP {{tp|p=25051011|t=2014. TNF-alpha mediated increase of HIF-1alpha inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI) |pdf=|usr=}}{{25051011}} gab.com Text TNF-alpha mediated increase of HIF-1alpha inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI) JO: PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=25051011 #FOAvip Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function and increased pulmonary vascular permeability. Vasodilator-stimulated phosphoprotein (VASP) is widely associated with all types of modulations of cytoskeleton rearrangement-dependent cellular morphology and function, such as adhesion, shrinkage, and permeability. The present studies were conducted to investigate the effects and mechanisms by which tumor necrosis factor-alpha (TNF-alpha) increases the tight junction permeability in lung tissue associated with acute lung inflammation. After incubating A549 cells for 24 hours with different concentrations (0-100 ng/mL) of TNF-alpha, 0.1 to 8 ng/mL TNF-alpha exhibited no significant effect on cell viability compared with the 0 ng/mL TNF-alpha group (control group). However, 10 ng/mL and 100 ng/mL TNF-alpha dramatically inhibited the viability of A549 cells compared with the control group (*p<0.05). Monolayer cell permeability assay results indicated that A549 cells incubated with 10 ng/mL TNF-alpha for 24 hours displayed significantly increased cell permeability (*p<0.05). Moreover, the inhibition of VASP expression increased the cell permeability (*p<0.05). Pretreating A549 cells with cobalt chloride (to mimic a hypoxia environment) increased protein expression level of hypoxia inducible factor-1alpha (HIF-1alpha) (*p<0.05), whereas protein expression level of VASP decreased significantly (*p<0.05). In LPS-induced ALI mice, the concentrations of TNF-alpha in lung tissues and serum significantly increased at one hour, and the value reached a peak at four hours. Moreover, the Evans Blue absorption value of the mouse lung tissues reached a peak at four hours. The HIF-1alpha protein expression level in mouse lung tissues increased significantly at four hours and eight hours (**p<0.001), whereas the VASP protein expression level decreased significantly (**p<0.01). Taken together, our data demonstrate that HIF-1alpha acts downstream of TNF-alpha to inhibit VASP expression and to modulate the acute pulmonary inflammation process, and these molecules play an important role in the impairment of the alveolar-capillary barrier. Twit Text FOAVip TNF-alpha mediated increase of HIF-1alpha inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI) ????PLoS One http://www.kidney.de/pget.php?&tw=1&pmid=25051011 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25051011 #FOAvip English Wikipedia <ref>{{Cite pmid|25051011}}</ref> TNF-alpha mediated increase of HIF-1alpha inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI) #MMPMID25051011 Tang M; Tian Y; Li D; Lv J; Li Q; Kuang C; Hu P; Wang Y; Wang J; Su K; Wei L PLoS One 2014[]; 9 (7): e102967 PMID25051011show ga Acute lung injury (ALI) is an inflammatory disorder associated with reduced alveolar-capillary barrier function and increased pulmonary vascular permeability. Vasodilator-stimulated phosphoprotein (VASP) is widely associated with all types of modulations of cytoskeleton rearrangement-dependent cellular morphology and function, such as adhesion, shrinkage, and permeability. The present studies were conducted to investigate the effects and mechanisms by which tumor necrosis factor-alpha (TNF-alpha) increases the tight junction permeability in lung tissue associated with acute lung inflammation. After incubating A549 cells for 24 hours with different concentrations (0-100 ng/mL) of TNF-alpha, 0.1 to 8 ng/mL TNF-alpha exhibited no significant effect on cell viability compared with the 0 ng/mL TNF-alpha group (control group). However, 10 ng/mL and 100 ng/mL TNF-alpha dramatically inhibited the viability of A549 cells compared with the control group (*p<0.05). Monolayer cell permeability assay results indicated that A549 cells incubated with 10 ng/mL TNF-alpha for 24 hours displayed significantly increased cell permeability (*p<0.05). Moreover, the inhibition of VASP expression increased the cell permeability (*p<0.05). Pretreating A549 cells with cobalt chloride (to mimic a hypoxia environment) increased protein expression level of hypoxia inducible factor-1alpha (HIF-1alpha) (*p<0.05), whereas protein expression level of VASP decreased significantly (*p<0.05). In LPS-induced ALI mice, the concentrations of TNF-alpha in lung tissues and serum significantly increased at one hour, and the value reached a peak at four hours. Moreover, the Evans Blue absorption value of the mouse lung tissues reached a peak at four hours. The HIF-1alpha protein expression level in mouse lung tissues increased significantly at four hours and eight hours (**p<0.001), whereas the VASP protein expression level decreased significantly (**p<0.01). Taken together, our data demonstrate that HIF-1alpha acts downstream of TNF-alpha to inhibit VASP expression and to modulate the acute pulmonary inflammation process, and these molecules play an important role in the impairment of the alveolar-capillary barrier. |Acute Lung Injury/chemically induced/*genetics/physiopathology[MESH] |Animals[MESH] |Blotting, Western[MESH] |Capillaries/*metabolism/physiopathology[MESH] |Cell Adhesion Molecules/*genetics/metabolism[MESH] |Cell Line, Tumor[MESH] |Cell Membrane Permeability/drug effects/genetics[MESH] |Cell Survival/drug effects/genetics[MESH] |Dose-Response Relationship, Drug[MESH] |Gene Expression/*drug effects[MESH] |Humans[MESH] |Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism[MESH] |Lipopolysaccharides[MESH] |Mice, Inbred BALB C[MESH] |Microfilament Proteins/*genetics/metabolism[MESH] |Phosphoproteins/*genetics/metabolism[MESH] |Pulmonary Alveoli/blood supply/metabolism/physiopathology[MESH] |RNA Interference[MESH] |Reverse Transcriptase Polymerase Chain Reaction[MESH]TNF-alpha mediated increase of HIF-1alpha inhibits VASP expression, wh(epmc).pdf DeepDyve Pubget Overpricing