Superoxide radicals increase transforming growth factor-β1 and collagen release from human lung fibroblasts via cellular influx through chloride channels

Qi, Shusen; Hartog, G.J.M. den; Bast, Aalt

doi:10.1016/j.taap.2009.02.019

Cited by 52 publications

(34 citation statements)

References 31 publications

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“…Heme-induced TGF-b reduction may involve ROS production rather than binding to a specific receptor. Recent studies have shown that superoxide anions increase the release of TGF-b1 and collagen from human lung fibroblasts (55). In our study, enhanced SOD-1 secretion could scavenge superoxide radicals, negatively impacting the production of TGF-b.…”

Section: Discussionsupporting

confidence: 54%

Heme Impairs Prostaglandin E2 and TGF-β Production by Human Mononuclear Cells via Cu/Zn Superoxide Dismutase: Insight into the Pathogenesis of Severe Malaria

Andrade

Araújo-Santos

Luz

et al. 2010

The Journal of Immunology

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In many hemolytic disorders, such as malaria, the release of free heme has been involved in the triggering of oxidative stress and tissue damage. Patients presenting with severe forms of malaria commonly have impaired regulatory responses. Although intriguing, there is scarce data about the involvement of heme on the regulation of immune responses. In this study, we investigated the relation of free heme and the suppression of anti-inflammatory mediators such as PGE2 and TGF-β in human vivax malaria. Patients with severe disease presented higher hemolysis and higher plasma concentrations of Cu/Zn superoxide dismutase (SOD-1) and lower concentrations of PGE2 and TGF-β than those with mild disease. In addition, there was a positive correlation between SOD-1 concentrations and plasma levels of TNF-α. During antimalaria treatment, the concentrations of plasma SOD-1 reduced whereas PGE2 and TGF-β increased in the individuals severely ill. Using an in vitro model with human mononuclear cells, we demonstrated that the heme effect on the impairment of the production of PGE2 and TGF-β partially involves heme binding to CD14 and depends on the production of SOD-1. Aside from furthering the current knowledge about the pathogenesis of vivax malaria, the present results may represent a general mechanism for hemolytic diseases and could be useful for future studies of therapeutic approaches.

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Section: Discussionsupporting

confidence: 54%

Heme Impairs Prostaglandin E2 and TGF-β Production by Human Mononuclear Cells via Cu/Zn Superoxide Dismutase: Insight into the Pathogenesis of Severe Malaria

Andrade

Araújo-Santos

Luz

et al. 2010

The Journal of Immunology

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“…ROS are known to be important in TGF-b signaling through a number of mechanisms. Superoxide radicals increase TGF-b transcription in alveolar epithelial cells (14) and promote TGF-b activity and collagen deposition from human lung fibroblasts (15). Mitochondrial ROS have recently been shown to be required for downstream TGFb 16 signaling, and mitochondrial dysfunction is a feature of asthmatic airway cells (17)(18)(19).…”

mentioning

confidence: 99%

Mitochondrial-Targeted Antioxidant Therapy Decreases Transforming Growth Factor-β–Mediated Collagen Production in a Murine Asthma Model

Jaffer¹,

Carter

Sanders³

et al. 2015

Am J Respir Cell Mol Biol

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Asthma is a disease of acute and chronic inflammation in which cytokines play a critical role in orchestrating the allergic inflammatory response. IL-13 and transforming growth factor (TGF)-b promote fibrotic airway remodeling, a major contributor to disease severity. Improved understanding is needed, because current therapies are inadequate for suppressing development of airway fibrosis. IL-13 is known to stimulate respiratory epithelial cells to produce TGF-b, but the mechanism through which this occurs is unknown. Here, we tested the hypothesis that reactive oxygen species (ROS) are a critical signaling intermediary between IL-13 or allergen stimulation and TGF-b-dependent airway remodeling. We used cultured human bronchial epithelial cells and an in vivo mouse model of allergic asthma to map a pathway where allergens enhanced mitochondrial ROS, which is an essential upstream signal for TGF-b activation and enhanced collagen production and deposition in airway fibroblasts. We show that mitochondria in airway epithelium are an essential source of ROS that activate TGF-b expression and activity. TGF-b from airway epithelium stimulates collagen expression in fibroblasts, contributing to an early fibrotic response to allergen exposure in cultured human airway cells and in ovalbumin-challenged mice. Treatment with the mitochondrialtargeted antioxidant, (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (mitoTEMPO), significantly attenuated mitochondrial ROS, TGF-b, and collagen deposition in OVA-challenged mice and in cultured human epithelial cells. Our findings suggest that mitochondria are a critical source of ROS for promoting TGF-b activity that contributes to airway remodeling in allergic asthma. Mitochondrial-targeted antioxidants may be a novel approach for future asthma therapies.

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“…Qi et al [66] reported that superoxide toxicity could activate human lung fibroblasts, which play a key role in the development of pulmonary fibrosis. In this study, O 2…”

Section: Discussionmentioning

confidence: 99%

The role of nitric oxide during healing of trauma to the skeletal muscle

et al. 2010

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Superoxide radicals increase transforming growth factor-β1 and collagen release from human lung fibroblasts via cellular influx through chloride channels

Cited by 52 publications

References 31 publications

Heme Impairs Prostaglandin E2 and TGF-β Production by Human Mononuclear Cells via Cu/Zn Superoxide Dismutase: Insight into the Pathogenesis of Severe Malaria

Heme Impairs Prostaglandin E2 and TGF-β Production by Human Mononuclear Cells via Cu/Zn Superoxide Dismutase: Insight into the Pathogenesis of Severe Malaria

Mitochondrial-Targeted Antioxidant Therapy Decreases Transforming Growth Factor-β–Mediated Collagen Production in a Murine Asthma Model

The role of nitric oxide during healing of trauma to the skeletal muscle

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