New Developments in the Therapy of Pulmonary Fibrosis

“…Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia of unknown causes and has poor prognosis [1,2]. Patients with IPF could be treated with steroids or immunosuppressants to ameliorate the inflammation that occurs early in the course of the disease, but these drugs do not improve their survival [3].…”

Section: Introductionmentioning

confidence: 99%

Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin

et al. 2011

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BackgroundCluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69-/-) mice.MethodsThe mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi). Lung inflammation in the acute phase (7 dpi) was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor β1 (TGF-β1) in the lungs of BLM-treated mice.ResultsCD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1) loss of body weight, (2) wet/dry ratio of lung, (3) cytokine levels in BALF, (4) histological evidence of lung injury, (5) lung collagen deposition, and (6) TGF-β1 mRNA expression in the lung.ConclusionThe present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.

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“…Mechanisms of drug-induced PF are mostly unknown; however, evidence suggests that the inflammasome may play a role. For example, bleomycin has been used to induce PF in murine models in order to better understand molecular mechanisms [23]. It has been demonstrated that bleomycin-induced lung inflammation and remodeling is largely mediated by uric acid, which is released from dying cells, upon injury or insult [24].…”

Section: Introductionmentioning

confidence: 99%

Potential Role of the Inflammasome-Derived Inflammatory Cytokines in Pulmonary Fibrosis

2011

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Pulmonary fibrosis is a progressive, disabling disease with mortality rates that appear to be increasing in the western population, including the USA. There are over 140 known causes of pulmonary fibrosis as well as many unknown causes. Treatment options for this disease are limited due to poor understanding of the molecular mechanisms of the disease progression. However, recent progress in inflammasome research has greatly contributed to our understanding of its role in inflammation and fibrosis development. The inflammasome is a multiprotein complex that is an important component of both the innate and adaptive immune systems. Activation of proinflammatory cytokines following inflammasome assembly, such as IL-1β and IL-18, has been associated with development of PF. In addition, components of the inflammasome complex itself, such as the adaptor protein ASC have been associated with PF development. Recent evidence suggesting that the fibrotic process can be reversed via blockade of pathways associated with inflammasome activity may provide hope for future drug strategies. In this paper we will give an introduction to pulmonary fibrosis and its known causes. In addition, we will discuss the importance of the inflammasome in the development of pulmonary fibrosis as well as discuss potential future treatment options.

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New Developments in the Therapy of Pulmonary Fibrosis

Cited by 10 publications

References 255 publications

Cutting edge: FasL+ immune cells promote resolution of fibrosis

Cutting edge: FasL+ immune cells promote resolution of fibrosis

Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin

Potential Role of the Inflammasome-Derived Inflammatory Cytokines in Pulmonary Fibrosis

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