TH2 Cytokine-enhanced and TGF-β-enhanced vascular endothelial growth factor production by cultured human airway smooth muscle cells is attenuated by IFN-γ and corticosteroids

Wen, Fu Qiang; Liu, Xiangde; Manda, Winfred; Terasaki, Yusuke; Kobayashi, Tetsu; Abe, Shinji; Fang, Qiuhong; Ertl, Ronald F.; Manouilova, Lidia S.; Rennard, Stephen I.

doi:10.1067/mai.2003.1455

Cited by 113 publications

(91 citation statements)

References 49 publications

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“…Several cell populations produce VEGF including CD34 + cells, macrophages, eosinophils [50], mast cells [47,50] fibroblasts [51] and ASM cells [26]. Interestingly, VEGF production by airway structural cells are induced by T H 17 cells [52] and suppressed by T H 1 cells [53]. Increased protein levels of VEGF are observed in bronchoalveolar lavage fluid (BALf), sputum and bronchial biopsies of asthma and COPD patients [11,13,48,54].…”

Section: Angiogenesis and Vascular Endothelial Growth Factormentioning

confidence: 99%

Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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In chronic lung disorders such as in asthma and chronic obstructive pulmonary disease (COPD) there is increased bronchial angiogenesis and remodelling of pulmonary vessels culminating to altered bronchial and pulmonary circulation. The involvement of residential cells such as endothelial cells, smooth muscle cells and pulmonary fibroblasts, all appear to have a crucial role in the progression of vascular inflammation and remodelling. The regulatory abnormalities, growth factors and mediators implicated in the pulmonary vascular changes of asthma and COPD subjects and potential therapeutic targets have been described in this review.

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Section: Angiogenesis and Vascular Endothelial Growth Factormentioning

confidence: 99%

Pulmonary vascular changes in asthma and COPD

Harkness

Kanabar

Sharma

et al. 2014

Pulmonary Pharmacology & Therapeutics

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“…It has been suggested that bronchial biopsies from atopic asthmatics compared with atopic control subjects exhibit increased expression of IL-4␣ mRNA and protein in the epithelium, subepithelium, and EC layer (31). There is evidence that Th2 cytokines (IL-4 and IL-13) induce VEGF from human airway smooth muscle cells (SMCs) (24,25).…”

Section: Il-4 Is Proangiogenic In the Lungmentioning

confidence: 99%

“…IL-4 is present at high levels in tissues of patients with chronic inflammatory diseases, including atherosclerotic lesions (17)(18)(19). Evidence indicates that IL-4 may play a role in vascular endothelial function through the induction of inflammatory responses, such as up-regulation of VCAM-1 (20 -22), MCP-1 (23), and vascular endothelial growth factor (VEGF) 3 (24,25), which is one of the most potent multifunctional angiogenic factors.…”

Section: Il-4 Is Proangiogenic In the Lungmentioning

confidence: 99%

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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“…Inflammatory cytokines such as interleukin-1␤ and transforming growth factor-␤ increased VEGF release in human cholangiocellular carcinoma cells, synovial fibroblasts, cardiac myocytes, and airway smooth muscle cells (11)(12)(13)(14). We have previously shown that the pro-inflammatory asthma mediator, bradykinin, increased VEGF production in human airway smooth muscle cells (HASMC) (15).…”

Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%