IL-4-induced Oxidative Stress Upregulates VCAM-1 Gene Expression in Human Endothelial Cells

Lee, Yong Woo; Kühn, Hartmut; Hennig, Bernhard; Neish, Andrew S.; Toborek, Michał

doi:10.1006/jmcc.2000.1278

Cited by 141 publications

(109 citation statements)

References 49 publications

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“…IL-4 may also be considered as a pro-oxidative cytokine that can increase the oxidative potential of target cells (21). A number of in vitro cellular biology data are consistent with the proatherogenic effect of IL-4.…”

Section: Il-4 Is Proangiogenic In the Lungmentioning

confidence: 86%

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

Yamaji-Kegan

Angelini

et al. 2009

The Journal of Immunology

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IL-4-mediated proangiogenic and proinflammatory vascular responses have been implicated in the pathogenesis of chronic lung diseases such as asthma. Although it is well known that hypoxia induces pulmonary angiogenesis and vascular alterations, the underlying mechanism of IL-4 on the pulmonary vasculature under hypoxic conditions remains unknown. In this context, we designed the present study to determine the functional importance of IL-4 for pulmonary angiogenesis under hypoxic conditions using IL-4 knockout (KO) animals. Our results show that hypoxia significantly increased IL-4Rα expression in wild-type (WT) control lungs. Even though hypoxia significantly up-regulated vascular endothelial growth factor (VEGF) receptor expression in the lungs of both genotypes, hypoxia-induced VEGF, VCAM-1, HIF-1α, and ERK phosphorylation were significantly diminished in IL-4 KO lungs as compared with WT control lungs. In addition, hypoxia-induced pulmonary angiogenesis and proliferating activities in the airway and pulmonary artery were significantly suppressed in IL-4 KO lungs as compared with WT control lungs. We also isolated primary lung fibroblasts from these genotypes and stimulated these cells with hypoxia. Hypoxia-induced VEGF production was significantly suppressed in lung fibroblasts from IL-4 KO mice. These in vitro results are in accordance with the in vivo data. Furthermore, we observed a significant increase of hypoxia-induced pulmonary angiogenesis in STAT6 KO mice similar to that in WT controls. In conclusion, IL-4 has proangiogenic properties in the lung under hypoxic conditions via the VEGF pathway, and this is independent of the STAT6 pathway.

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Section: Il-4 Is Proangiogenic In the Lungmentioning

confidence: 86%

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

Yamaji-Kegan

Angelini

et al. 2009

The Journal of Immunology

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“…TNF-α and IFNγ can induce an activation of STAT-1 and STAT-3 in astrocytes [20][21][22]. Several lines of evidence suggest that AP-1 and NF-κB mediate the expression of ICAM-1 and VCAM-1 in several cell types [12,[23][24][25][26][27]. Furthermore, NF-κB DNA binding activity and luciferase repoter activity were inhibited by PDMP in LPS and IFNγ-treated astrocytes [6].…”

Section: Discussionmentioning

confidence: 99%

Lactosylceramide Mediates the Expression of Adhesion Molecules in TNF-α and IFNγ-stimulated Primary Cultured Astrocytes

Lee

Kim

Park

et al. 2011

Korean J Physiol Pharmacol

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“…VCAM-1 is involved in the recruitment of mononuclear blood cells into the vascular wall (25). Soluble VCAM-1 in plasma is derived from shedding of endothelial cells and has also been related to endothelial dysfunction (26). In the absence of significant excretion of sVCAM-1 in the urine (27), plasma sVCAM-1 concentration can be regarded as a reflection of endothelial release.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Dysfunction Contributes to Renal Function–Associated Cardiovascular Mortality in a Population with Mild Renal Insufficiency

Stam¹,

Guldener²,

Becker³

et al. 2006

Journal of the American Society of Nephrology

227

169

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Mildly impaired renal function is associated with cardiovascular morbidity and mortality. There are indications that endothelial dysfunction and/or chronic inflammation, which play an important role in atherothrombosis, are present in early stages of renal insufficiency. This study investigated whether and to which extent endothelial dysfunction and inflammation were related to renal function and contributed to renal function-associated cardiovascular mortality in a population-based cohort (n ‫؍‬ 613), aged 50 to 75 yr, that was followed with a median duration of 12.5 yr. During follow-up, 192 individuals died (67 of cardiovascular causes). At baseline, renal function was estimated with serum creatinine, the Cockcroft-Gault formula, and the Modification of Diet in Renal Disease equation of GFR (eGFR). Endothelial function was estimated by plasma von Willebrand factor, soluble vascular cell adhesion molecule-1, and the urinary albumin-creatinine ratio. Inflammatory activity was estimated by plasma C-reactive protein and soluble intercellular adhesion molecule-1. Renal function was mildly impaired (mean eGFR 68 ؎ 12 ml/min per 1.73 m 2 ) and independently associated with von Willebrand factor (standardized ␤ ؊0.09; 95% confidence interval [CI] ؊0.18 to ؊0.002; P < 0.05), soluble vascular cell adhesion molecule-1 (standardized ␤ ؊0.14; 95% CI ؊0.22 to ؊0.05; P < 0.01), and albumin-creatinine ratio (standardized ␤ ؊0.15; 95% CI ؊0.23 to ؊0.08; P < 0.001) but not with markers of inflammatory activity. Renal function was inversely associated with cardiovascular and all-cause mortality. The relative risk for cardiovascular mortality but not all-cause mortality associated with renal function decreased from 1.22 to 1.12 per 5 ml/min per 1.73 m 2 decrease of eGFR after adjustment for markers of endothelial dysfunction. In conclusion, endothelial dysfunction was related to renal function and contributed to the excess in cardiovascular mortality in this population-based cohort with mild renal insufficiency.

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IL-4-induced Oxidative Stress Upregulates VCAM-1 Gene Expression in Human Endothelial Cells

Cited by 141 publications

References 49 publications

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

IL-4 Is Proangiogenic in the Lung under Hypoxic Conditions

Lactosylceramide Mediates the Expression of Adhesion Molecules in TNF-α and IFNγ-stimulated Primary Cultured Astrocytes

Endothelial Dysfunction Contributes to Renal Function–Associated Cardiovascular Mortality in a Population with Mild Renal Insufficiency

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