Bleomycin induced lung fibrosis increases work of breathing in the mouse

Phillips, Jonathan E.; Peng, Ruoqi; Burns, Lisa; Harmatz, Paul; Garrido, Rosario; Tyagi, Gaurav; Fine, Jay S.; Stevenson, Christopher S.

doi:10.1016/j.pupt.2011.10.001

Cited by 35 publications

(39 citation statements)

References 18 publications

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“…Animals were administered bleomycin (2 U/kg) or normal saline as described previously (Phillips et al, 2011). Animals were fed normal chow diet (Purina Rodent Chow #5001; Purina, St. Louis, MO) or Purina Rodent Chow #5001 mixed with JQ-1 and a coloring dye to identify the correct formulation for each group.…”

Section: Administration Of Jq-1 and Bleomycinmentioning

confidence: 99%

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BET Bromodomain Proteins Mediate Downstream Signaling Events following Growth Factor Stimulation in Human Lung Fibroblasts and Are Involved in Bleomycin-Induced Pulmonary Fibrosis

et al. 2012

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Epigenetic alterations, such as histone acetylation, regulate the signaling outcomes and phenotypic responses of fibroblasts after growth factor stimulation. The bromodomain and extraterminal domain-containing proteins (Brd) bind to acetylated histone residues, resulting in recruitment of components of the transcriptional machinery and subsequent gene transcription. Given the central importance of fibroblasts in tissue fibrosis, this study sought to determine the role of Brd proteins in human lung fibroblasts (LFs) after growth factor stimulation and in the murine bleomycin model of lung fibrosis. Using small interfering RNA against human Brd2 and Brd4 and pharmacologic Brd inhibitors, this study found that Brd2 and Brd4 are essential in mediating the phenotypic responses of LFs downstream of multiple growth factor pathways. Growth factor stimulation of LFs causes increased histone acetylation, association of Brd4 with growth factor-responsive genes, and enhanced transcription of these genes that could be attenuated with pharmacologic Brd inhibitors. Of note, lung fibrosis induced after intratracheal bleomycin challenge in mice could be prevented by pretreatment of animals with pharmacologic inhibitors of Brd proteins. This study is the first demonstration of a role for Brd2 and Brd4 proteins in mediating the responses of LFs after growth factor stimulation and in driving the induction of lung fibrosis in mice in response to bleomycin challenge.

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Section: Administration Of Jq-1 and Bleomycinmentioning

confidence: 99%

“…Subsequently bronchoalveolar lavage (BAL) was performed, and total cell counts were performed as previously described (Phillips et al, 2011). For the analysis of 4-hydroxyproline, BAL fluid samples were extracted with acetonitrile at a volume of 1:6, respectively.…”

Section: Assessment Of Inflammation and Fibrosismentioning

confidence: 99%

BET Bromodomain Proteins Mediate Downstream Signaling Events following Growth Factor Stimulation in Human Lung Fibroblasts and Are Involved in Bleomycin-Induced Pulmonary Fibrosis

et al. 2012

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“…[2][3][4] To date, no treatment has been clearly shown to reverse the fibrosis after the development of pulmonary fibrosis, 7,8 whereas there are also studies indicating the prevention or slowing down of fibrosis development via use of certain drugs prior to or concomitant with bleomycin treatment including glucocorticoids, prostaglandins, surfactants, prostacyclin analogues. [9][10][11] In our case, there was no response to treatment with inhaler surfactant, inhaler prostacyclin, and IV NSAIDs one month after the use of bleomycin.…”

Section: Discussionmentioning

confidence: 99%

“…1 Use of bleomycin in squamous cell carcinoma, lymphoma, testicular carcinoma and malignant pleural effusion has been associated with the development of pulmonary fibrosis in 1% of cases. 2 Development of alveolitis in the early period of bleomycin-induced inflammation and fibrosis due to chronic inflammation have been demonstrated. 3,4 In the acute phase, an increase in the prothrombotic and procoagulant activity while a decrease in the fibrinolytic activity occurs in the bronchoalveolar compartment.…”

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confidence: 99%

Bleomycin-Induced Pulmonary Fibrosis, Severe Hypoxia and Intracardiac Air Embolism: Case Report

Güçyetmez¹,

Ogan²,

Güder³

et al. 2015

Turkiye Klinikleri J Case Rep

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12leomycin sulphate is a mixture of cytotoxic glycopeptide antibiotics isolated from a strain of Streptomyces verticillus.1 Use of bleomycin in squamous cell carcinoma, lymphoma, testicular carcinoma and malignant pleural effusion has been associated with the development of pulmonary fibrosis in 1% of cases.2 Development of alveolitis in the early period of bleomycin-induced inflammation and fibrosis due to chronic inflammation have been demonstrated. 3,4 In the acute phase, an increase in the prothrombotic and procoagulant activity while a decrease in the fibrinolytic activity occurs in the bronchoalveolar compartment.5 Fibroblast deposition in the lung capillary endothelial cells, possibly through endothelial-mesenchymal transition was also shown in bleomycin-induced pulmonary fibrosis. 6 Herein we report development of pulmonary fibrosis following bleomycin treatment in Bleomycin-Induced Pulmonary Fibrosis, Severe Hypoxia and Intracardiac Air Embolism:Case Report A AB BS ST TR RA AC CT T Bleomycin sulphate is a mixture of cytotoxic glycopeptide antibiotics isolated from a strain of Streptomyces verticillus. Use of bleomycin in squamous cell carcinoma, lymphoma, testicular carcinoma and malignant pleural effusion has been associated with the development of pulmonary fibrosis in 1% of cases. Bleomycin-induced pulmonary fibrosis results in severe hypoxemia due to inflammation that develops in the alveolar capillary membrane and this patients are associated with less-than-expected response to medical treatment besides the likelihood of complications related to mechanical ventilation. Herein, we report development of severe hypoxemia and intracardiac air embolism under mechanical ventilation who has no response to medical treatment in a 39-year-old male patient following bleomycin treatment.K Ke ey y W Wo or rd ds s: : Bleomycin; pulmonary fibrosis; embolism, air Ö ÖZ ZE ET T Bleomisin sülfat, Streptomyces verticillus'un bir alt türünden izole edilmiş sitotoksik glikopeptid antibiyotiklerin bir karışımıdır. Skuamöz hücreli karsinom, lenfoma, testiküler karsinom ve malign plevral effüzyonda kullanılan bleomisine bağlı %1 olguda pulmoner fibrozis gelişmektedir.Bleomisin'e bağlı gelişen pulmoner fibrozis alveolokapiller membranda inflamasyon oluşumuna bağlı ciddi hipoksi ile sonuçlanır. Bu hastalarda medikal tedaviye yanıt beklenenden azdır ayrıca mekanik ventilasyona bağlı olası komplikasyonlar gelişmektedir. Bleomisin tedavisini takiben pulmoner fibrozis gelişen, medikal tedavilere yanıt alınamayan, ciddi hipoksi ile seyreden ve mekanik ventilasyon altında intrakardiyak hava embolisi gelişen 39 yaşındaki erkek olgumuz sunulmuştur.A An na ah ht ta ar r K Ke el li im me el le er r: : Bileomisin; pulmoner fibrozis; emboli, hava T Tu ur rk ki iy ye e K Kl li in ni ik kl le er ri i J J C Ca as se e R Re ep p 2 20 01 15 5; ;2 23 3( (1 1) ): :1 12 2--5 5

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“…Immunohistochemistry of collagen I was performed as described previously (Phillips et al, 2012). Briefly, antigen retrieval was performed in citrate buffer (pH=6.0) and microwaved for 20 minutes, then the slices were incubated with an anti-collagen I 7 antibody (rabbit polyclonal, Genetex Inc., Irvine, USA) to visualize the lung fibrosis content.…”

Section: Hande and Immunohistochemistry Staining Of Collagen Imentioning

confidence: 99%

Neonatal bronchopulmonary dysplasia increases neuronal apoptosis in the hippocampus through the HIF-1α and p53 pathways

Yin

Lin

Ping

et al. 2016

Respiratory Physiology & Neurobiology

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Bleomycin induced lung fibrosis increases work of breathing in the mouse

Cited by 35 publications

References 18 publications

BET Bromodomain Proteins Mediate Downstream Signaling Events following Growth Factor Stimulation in Human Lung Fibroblasts and Are Involved in Bleomycin-Induced Pulmonary Fibrosis

BET Bromodomain Proteins Mediate Downstream Signaling Events following Growth Factor Stimulation in Human Lung Fibroblasts and Are Involved in Bleomycin-Induced Pulmonary Fibrosis

Bleomycin-Induced Pulmonary Fibrosis, Severe Hypoxia and Intracardiac Air Embolism: Case Report

Neonatal bronchopulmonary dysplasia increases neuronal apoptosis in the hippocampus through the HIF-1α and p53 pathways

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