Palifermin Induces Alveolar Maintenance Programs in Emphysematous Mice

Yildirim, Ali Önder; Muyal, Vandana; Gorcsan, John; Müller, Bernd; Seifart, Carola; Kasper, Michael; Fehrenbach, Heinz

doi:10.1164/rccm.200804-573oc

Cited by 55 publications

(49 citation statements)

References 66 publications

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“…Moreover, soluble elastin does not allow any conclusions to be drawn about the deposition of (insoluble) elastin as a component of the extracellular scaffold of alveolar septa. Although the elastase-induced rodent model is highly specific and has clear limitations in the investigation of the pathogenesis of the human disease, it can be used to study potential effects of therapeutics on alveolar septal maintenance and regeneration [39,40]. Our findings are consistent with data obtained in a canine model of compensatory lung growth following right-sided pneumonectomy.…”

Section: Discussionsupporting

confidence: 85%

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages

Seifart

Muyal

Plagens

et al. 2011

European Respiratory Journal

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All-trans retinoic acid (ATRA) is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase model and hypothesised that beneficial effects should be reflected by increased alveolar surface area, elastin expression and downregulation of inflammatory mediators and matrix metalloproteinases (MMPs).Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 mg?kg -1 body weight)versus olive oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA-or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by alveolar epithelial cells type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1 + :ED2 + macrophages. Bronchoalveolar lavage (BAL) cells exhibited a proinflammatory state and high expression of interleukin-1b, cytokine-induced neutrophil chemoattractant-1, tumour necrosis factor-a, nuclear factor-kB, MMP-2, MMP-9, MMP-12, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in emphysema, with ATRA exerting only few effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.

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Section: Discussionsupporting

confidence: 85%

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages

Seifart

Muyal

Plagens

et al. 2011

European Respiratory Journal

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“…Emphysema was induced in mice by oropharyngeal application of porcine pancreatic elastase (PPE, 80 U/kg body wt in 80 l volume) as previously described (59). Control mice received 80 l of sterile PBS.…”

Section: Methodsmentioning

confidence: 99%

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

John-Schuster

Hager

Conlon

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…14,15 Palifermin might also have a protective action on endothelium and fibroblasts. 16,17 To conclude, this study failed to detect any clinically relevant impact of palifermin on intestinal mucositis. However, the Type of SCT Autologous Autologous (b): General outcome measure of neutrophils, citrulline, inflammation and bacteraemia…”

mentioning

confidence: 63%

Impact of palifermin on intestinal mucositis of HSCT recipients after BEAM

Herbers

Velden

Haan

et al. 2013

Bone Marrow Transplant

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Palifermin Induces Alveolar Maintenance Programs in Emphysematous Mice

Abstract: Our data demonstrate that therapeutic application of DeltaN23-KGF has the potential to induce alveolar maintenance programs in emphysematous lungs and suggest that the regenerative effect on interstitial tissue is linked to AE2 cell-derived TGF-beta1.

Cited by 55 publications

References 66 publications

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages

Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

Impact of palifermin on intestinal mucositis of HSCT recipients after BEAM

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