Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells.

Sesko, Ann; Cabot, Myles C.; Mossman, Brooke T.

doi:10.1073/pnas.87.19.7385

Cited by 35 publications

(19 citation statements)

References 24 publications

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“…Likewise, asbestos is an agent causing cell injury at higher concentrations and proliferation at lower concentrations in airway epithelial cells in vitro (35). The fact that myeloperoxidase and asbestos might cooperatively contribute to oxidant-associated cell damage is supported by many observations showing that these agents increase oxidative stress in lung tissue (17,34).…”

Section: Discussionmentioning

confidence: 98%

Asbestos-Induced Lung Inflammation and Epithelial Cell Proliferation Are Altered in Myeloperoxidase-Null Mice

Haegens¹,

Vliet²,

Butnor³

et al. 2005

Cancer Research

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Asbestos fibers are carcinogens causing oxidative stress and inflammation, but the sources and ramifications of oxidant production by asbestos are poorly understood. Here, we show that inhaled chrysotile asbestos fibers cause increased myeloperoxidase activity in bronchoalveolar lavage fluids (BALF) and myeloperoxidase immunoreactivity in epithelial cells lining distal bronchioles and alveolar ducts, sites of initial lung deposition of asbestos fibers. In comparison with sham mice, asbestos-exposed myeloperoxidase-null (MPOÀ/À) and normal (MPO+/+) mice exhibited comparable increases in polymorphonuclear leukocytes, predominately neutrophils, in BALF after 9 days of asbestos inhalation. Differential cell counts on BALF revealed decreased proportions of macrophages and increased lymphocytes in all mice exposed to asbestos, but numbers were decreased overall in asbestosexposed myeloperoxidase-null versus normal mice. Asbestosassociated lung inflammation in myeloperoxidase-null mice was reduced (P V 0.05) in comparison with normal asbestosexposed mice at 9 days. Decreased lung inflammation in asbestos-exposed myeloperoxidase-null mice at 9 days was accompanied by increases (P V 0.05) in Ki-67-and cyclin D1-positive immunoreactive cells, markers of cell cycle reentry, in the distal bronchiolar epithelium. Asbestos-induced epithelial cell proliferation in myeloperoxidase-null mice at 30 days was comparable to that found at 9 days. In contrast, inflammation and epithelial cell proliferation in asbestos-exposed normal mice increased over time. These results support the hypothesis that myeloperoxidase status modulates early asbestos-induced oxidative stress, epithelial cell proliferation, and inflammation.

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Section: Discussionmentioning

confidence: 98%

Asbestos-Induced Lung Inflammation and Epithelial Cell Proliferation Are Altered in Myeloperoxidase-Null Mice

Haegens¹,

Vliet²,

Butnor³

et al. 2005

Cancer Research

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“…3). Be nase C and inositol phospholipids in tracheal epithelial cells (25,26). On the other hand, inorganic particulates could stimulate the production of cytokines that are known to selectively increase PDGF-Ra.…”

Section: Discussionmentioning

confidence: 99%

Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts.

Bonner

Goodell²,

Coin³

et al. 1993

J. Clin. Invest.

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PDGF isoforms have been postulated to serve as mediators of fibroblast proliferation and chemotaxis during lung fibrogenesis induced by asbestos inhalation. We have studied the interaction of chrysotile asbestos fibers with rat lung fibroblasts (RLF) in vitro and the consequent changes in PDGF receptor mRNA expression, PDGF binding, and mitogenic activity of PDGF isoforms. Northern blot analysis revealed that mRNA for the PDGF-receptor a subtype (PDGF-Ra) on RLF was upregulated after a 24-h exposure to asbestos in culture (0.5-15 tug fibers/cm2). I125IIPDGF-BB receptor assays showed that normal RLF possess mainly PDGF-R,# and a paucity of PDGF-Ra. In agreement with the Northern data, saturation binding of I'25IIPDGF-BB to RLF exposed to asbestos demonstrated an -40% increase in binding sites accompanied by a twofold decrease in receptor affinity. Treating asbestos-exposed RLF with PDGF-AA, which binds only PDGF-Ra, blocked the PDGF binding sites that were upregulated by fiber exposure. PDGF-AA had increased mitogenic potency for fiber-exposed RLF, but PDGF-BB was a less potent mitogen for these RLF. Nonfibrogenic carbonyl iron spheres induced similar changes in PDGF growth responses. These data show that inorganic particulates alter the PDGF-Ra population on RLF without significant change in PDGF-Rfi. (J. Clin. Invest. 1993. 92:425-430.)

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“…We first showed that asbestos fibers, either directly or via production of reactive oxygen or nitrogen species, induced cell signaling events, including the production of diacylglycerol, hydrolysis of phosphatidylinositol, and activation of protein kinase C at the plasma membrane (17)(18)(19). These events were linked to increased expression of ornithine decarboxylase (ODC) (20), the enzyme responsible for the rate-limiting step in the synthesis of polyamines, a crucial step in cell proliferation induced by growth factors and phorbol ester tumor promoters.…”

Section: Oxidants and Asbestosmentioning

confidence: 99%

Asbestos, Lung Cancers, and Mesotheliomas

Heintz

Janssen–Heininger

Mossman

2010

Am J Respir Cell Mol Biol

160

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Fifteen years have passed since we published findings in the AJRCMB demonstrating that induction of early response fos/jun protooncogenes in rodent tracheal and mesothelial cells correlates with fibrous geometry and pathogenicity of asbestos. Our study was the first to suggest that the aberrant induction of signaling responses by crocidolite asbestos and erionite, a fibrous zeolite mineral associated with the development of malignant mesotheliomas (MMs) in areas of Turkey, led to altered gene expression. New data questioned the widely held belief at that time that the carcinogenic effects of asbestos in the development of lung cancer and MM were due to genotoxic or mutagenic effects. Later studies by our group revealed that proto-oncogene expression and several of the signaling pathways activated by asbestos were redox dependent, explaining why antioxidants and antioxidant enzymes were elevated in lung and pleura after exposure to asbestos and how they alleviated many of the phenotypic and functional effects of asbestos in vitro or after inhalation. Since these original studies, our efforts have expanded to understand the interface between asbestos-induced redox-dependent signal transduction cascades, the relationship between these pathways and cell fate, and the role of asbestos and cell interactions in development of asbestos-associated diseases. Of considerable significance is the fact that the signal transduction pathways activated by asbestos are also important in survival and chemoresistance of MMs and lung cancers. An understanding of the pathogenic features of asbestos fibers and dysregulation of signaling pathways allows strategies for the prevention and therapy of asbestos-related diseases.

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Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells.

Cited by 35 publications

References 24 publications

Asbestos-Induced Lung Inflammation and Epithelial Cell Proliferation Are Altered in Myeloperoxidase-Null Mice

Asbestos-Induced Lung Inflammation and Epithelial Cell Proliferation Are Altered in Myeloperoxidase-Null Mice

Chrysotile asbestos upregulates gene expression and production of alpha-receptors for platelet-derived growth factor (PDGF-AA) on rat lung fibroblasts.

Asbestos, Lung Cancers, and Mesotheliomas

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