Nitric oxide in the pathogenesis of diffuse pulmonary fibrosis

Hsu, Yi‐Chiang; Wang, Leng Fang; Chien, Yie W.

doi:10.1016/j.freeradbiomed.2006.11.031

Cited by 46 publications

(34 citation statements)

References 46 publications

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“…For example, in animal studies, reactive nitrogen intermediates stimulated production of TGF-␤. 40 Accordingly, we observed a significant increase in levels of TGF-␤ in BAL fluid from BMT mice at day 21 after infection ( Figure 6), and kinetic increases in nitrite and TGF-␤ are similar after infection (see Supplemental Figure S4 at http://ajp.amjpathol.org). It is also possible that the increased presence of neutrophils in the BMT mice contributed to the secretion of oxidants into the alveolar space.…”

mentioning

confidence: 62%

Severe Gammaherpesvirus-Induced Pneumonitis and Fibrosis in Syngeneic Bone Marrow Transplant Mice Is Related to Effects of Transforming Growth Factor-β

Coomes

Farmen

Wilke

et al. 2011

The American Journal of Pathology

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Pulmonary infections and pneumonitis occur frequently after hematopoietic stem cell transplantation. Using a syngeneic mouse model of bone marrow transplantation (BMT), we have previously demonstrated that BMT mice are more susceptible to acute gammaherpesvirus 68 (MHV-68) replication at day 7 after infection. By day 21, the virus is latent in lungs of BMT and control mice, and there is no difference in viral load. Despite similar latent viral load, BMT mice develop severe pneumonitis associated with reduced oxygen saturation, fibrosis, peripheral inflammation, hyaline membranes, and foamy alveolar macrophages, a phenotype that persists for 7 weeks after infection. BMT mice demonstrate increased bronchoalveolar lavage (BAL) cells, and this population is enriched in neutrophils and T cells. Alternatively, activated macrophages appear earlier than do classically activated macrophages. BAL fluid from BMT mice at day 21 after infection contains increased levels of hydrogen peroxide, nitrite, and transforming growth factor-␤ (TGF-␤). Mice expressing the dominant-negative transgene dn-TGF␤RII in multiple cell types were used as BMT donors. BMT mice with T-cell dnTGF␤RII are largely protected from the pneumonitis phenotype, whereas mice with CD11c-dnTGF␤RII BMT mice are only modestly protected from pneumonitis. Protection in BMT mice with T-cell dnTGF␤RII is associated with decreased TGF-␤ derived from parenchymal cells in the BAL fluid, lower nitrite levels, and reduced apoptosis, whereas alternatively activated macrophage markers are unchanged. (Am J Pathol

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mentioning

confidence: 62%

Severe Gammaherpesvirus-Induced Pneumonitis and Fibrosis in Syngeneic Bone Marrow Transplant Mice Is Related to Effects of Transforming Growth Factor-β

Coomes

Farmen

Wilke

et al. 2011

The American Journal of Pathology

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“…Previous studies have shown that acetaldehyde, the primary product of ethanol biotransformation, stimulates procollagen type I gene transcription via an increase in TGF-␤1 mRNA levels (5,11,46). It is well established that TGF-␤1 is not only capable of inducing collagen synthesis (5,32), but can reduce the rate of collagen degradation, resulting in an accumulation of collagen. For example, collagen is degraded by matrix metalloproteinases (MMPs), and the activity of MMPs is inhibited by tissue inhibitors of MMPs (TIMPs).…”

Section: Discussionmentioning

confidence: 99%

Repeated ethanol exposure during late gestation alters the maturation and innate immune status of the ovine fetal lung

Sozo¹,

O'Day²,

Maritz³

et al. 2009

American Journal of Physiology-Lung Cellular and Molecular Phys

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Little is known about the effects of fetal ethanol exposure on lung development. Our aim was to determine the effects of repeated ethanol exposure during late gestation on fetal lung growth, maturation, and inflammatory status. Pregnant ewes were chronically catheterized at 91 days of gestational age (DGA; term ϳ147 days). From 95-133 DGA, ewes were given a 1-h daily infusion of either 0.75 g ethanol/kg (n ϭ 9) or saline (n ϭ 8), with tissue collection at 134 DGA. Fetal lungs were examined for changes in tissue growth, structure, maturation, inflammation, and oxidative stress. Between treatment groups, there were no differences in lung weight, DNA and protein contents, percent proliferating and apoptotic cells, tissue and air-space fractions, alveolar number and mean linear intercept, septal thickness, type-II cell number and elastin content. Ethanol exposure caused a 75% increase in pulmonary collagen I ␣1 mRNA levels (P Ͻ 0.05) and a significant increase in collagen deposition. Surfactant protein (SP)-A and SP-B mRNA levels were approximately one third of control levels following ethanol exposure (P Ͻ 0.05). The mRNA levels of the proinflammatory cytokines interleukin (IL)-1␤ and IL-8 were also lower (P Ͻ 0.05) in ethanol-exposed fetuses compared with controls. Pulmonary malondialdehyde levels tended to be increased (P ϭ 0.07) in ethanolexposed fetuses. Daily exposure of the fetus to ethanol during the last third of gestation alters extracellular matrix deposition and surfactant protein gene expression, which could increase the risk of respiratory distress syndrome after birth. Changes to the innate immune status of the fetus could increase the susceptibility of the neonatal lungs to infection.

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“…Chronic airway inflammation was induced as previously described (10,17). Male Hartley guinea pigs (300 -400 g) were placed in a box coupled to an ultrasonic nebulizer (US-1000; ICEL), and an aerosol of ovalbumin (grade V, Sigma-Aldrich Chemical) diluted in 0.9% NaCl (normal saline) was generated for 15 min or until respiratory distress occurred.…”

Section: Methodsmentioning

confidence: 99%

Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

Angeli¹,

Prado²,

Xisto³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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Nitric oxide in the pathogenesis of diffuse pulmonary fibrosis

Cited by 46 publications

References 46 publications

Severe Gammaherpesvirus-Induced Pneumonitis and Fibrosis in Syngeneic Bone Marrow Transplant Mice Is Related to Effects of Transforming Growth Factor-β

Severe Gammaherpesvirus-Induced Pneumonitis and Fibrosis in Syngeneic Bone Marrow Transplant Mice Is Related to Effects of Transforming Growth Factor-β

Repeated ethanol exposure during late gestation alters the maturation and innate immune status of the ovine fetal lung

Effects of chronic l-NAME treatment lung tissue mechanics, eosinophilic and extracellular matrix responses induced by chronic pulmonary inflammation

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