Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice

Liu, Wei; Wan, Jing; Han, Jian; Li, Chen; Feng, Dandan; Yue, Shaojie; Huang, Yanhong; Chen, Yi; Cheng, Qing; Li, Yang; Luo, Ziqiang

doi:10.1186/1465-9921-14-101

Cited by 48 publications

(38 citation statements)

References 36 publications

(40 reference statements)

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“…In our study, we established the mouse pulmonary fibrosis model using a single intratracheal injection of bleomycin. Similar to previous observations, the lung tissue structural damage, inflammatory cells infiltration, and obvious edema were observed 7 days after bleomycin injection (Liu, Wan, Han, Li, Feng, Yue, Huang, Chen, Cheng, Li and Luo, 2013b). In addition, the Masson's trichrome stain results showed significant collagen deposition.…”

Section: Discussionsupporting

confidence: 90%

“…The mice were randomly divided into three groups: (1) intratracheal saline (normal group); (2) intratracheal bleomycin plus vehicle (BLM group); (3) intratracheal BLM plus TPPU treatment (BLM +TPPU group). The mouse model of PF was established by an intratracheal injection of bleomycin (5 mg/kg, Nippon Kayaku, Japan) according to a previous published protocol (Liu, et al, 2013b). All surgeries were performed under anesthesia with an intraperitoneal injection of sodium pentobarbital (30 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

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Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice

et al. 2015

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Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs, but not their diols, have anti-inflammatory properties, and inhibition of sEH might provide protective effects against inflammatory fibrosis. In this study, we tested the effects of a selected sEH inhibitor, 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea (TPPU), on bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model of PF was established by intratracheal injection of bleomycin, and TPPU was administered for 21 days after bleomycin injection. We found TPPU treatment improved the body weight loss and survival rate of bleomycin-stimulated mice. Histological examinations showed that TPPU treatment alleviated bleomycin-induced inflammation, and maintained alveolar structure of pulmonary tissues. TPPU also decreased bleomycin-induced deposition of collagen, and expression of the procollagen I mRNA in lung tissues of mice. TPPU decreased the TGF-β1, IL-1β and IL-6 levels in serum of bleomycin-stimulated mice. Moreover, TPPU inhibited proliferation, collagen synthesis of the mouse fibroblasts, and partially reversed TGF-β1-induced α-SMA expression. Our results indicated that inhibition of sEH attenuates bleomycin-induced inflammation, collagen deposition, and therefore prevents bleomycin-induced PF in mice model.

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Section: Discussionsupporting

confidence: 90%

Section: Methodsmentioning

confidence: 99%

Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice

et al. 2015

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“…In agreement with this notion are the findings that PEX13 knockdown in fibroblast induce activation of TGF-β1 signaling, increased ROS, collagen and IL-6 production. Several studies have reported that ROS and release of proinflammatory cytokines are the main triggers of TGF-β1 signaling pathway, shown also during the peak of inflammation on day 7 using the bleomycin-induced lung fibrosis mouse model (1,25). Interestingly, in our bleomycin model, the strongest down-regulation of peroxisomes is also observed during day 7 (Fig.…”

Section: Discussionsupporting

confidence: 58%

Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle inducing a higher fibrotic response via TGF-β signaling

Oruqaj

Karnati

Vijayan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Idiopathic pulmonary fibrosis (IPF) is a devastating disease, and its pathogenic mechanisms remain incompletely understood. Peroxisomes are known to be important in ROS and proinflammatory lipid degradation, and their deficiency induces liver fibrosis. However, altered peroxisome functions in IPF pathogenesis have never been investigated. By comparing peroxisome-related protein and gene expression in lung tissue and isolated lung fibroblasts between human control and IPF patients, we found that IPF lungs exhibited a significant down-regulation of peroxisomal biogenesis and metabolism (e.g., PEX13p and acyl-CoA oxidase 1). Moreover, in vivo the bleomycin-induced down-regulation of peroxisomes was abrogated in transforming growth factor beta (TGF-β) receptor II knockout mice indicating a role for TGF-β signaling in the regulation of peroxisomes. Furthermore, in vitro treatment of IPF fibroblasts with the profibrotic factors TGF-β1 or tumor necrosis factor alpha (TNF-α) was found to down-regulate peroxisomes via the AP-1 signaling pathway. Therefore, the molecular mechanisms by which reduced peroxisomal functions contribute to enhanced fibrosis were further studied. Direct down-regulation of PEX13 by RNAi induced the activation of Smad-dependent TGF-β signaling accompanied by increased ROS production and resulted in the release of cytokines (e.g., IL-6, TGF-β) and excessive production of collagen I and III. In contrast, treatment of fibroblasts with ciprofibrate or WY14643, PPAR-α activators, led to peroxisome proliferation and reduced the TGF-β–induced myofibroblast differentiation and collagen protein in IPF cells. Taken together, our findings suggest that compromised peroxisome activity might play an important role in the molecular pathogenesis of IPF and fibrosis progression, possibly by exacerbating pulmonary inflammation and intensifying the fibrotic response in the patients.

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“…CC16 has anti-inflammatory activities in various models of pulmonary inflammatory diseases other than COPD such as allergen-induced airway inflammation 107;108 , bleomycin-induced pulmonary inflammation 109;110 , and airway respiratory syncytial viral infections and inflammation in mice 111 . It is noteworthy that macrophages are required for emphysema development in mice 112 , and CC16 reduced lung macrophage counts in CS-exposed mice 90 .…”

Section: Club Cell Protein-16 (Cc16)mentioning

confidence: 99%

Club Cell Protein 16 (CC16) Augmentation: A Potential Disease-modifying Approach for Chronic Obstructive Pulmonary Disease (COPD)

Laucho-Contreras

Polverino

Tesfaigzi

et al. 2016

Expert Opinion on Therapeutic Targets

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Introduction Club cell protein 16 (CC16) is the most abundant protein in bronchoalveolar lavage fluid. CC16 has anti-inflammatory properties in smoke-exposed lungs, and chronic obstructive pulmonary disease (COPD) is associated with CC16 deficiency. Herein, we explored whether CC16 is a therapeutic target for COPD. Areas Covered We reviewed the literature on the factors that regulate airway CC16 expression, its biologic functions and its protective activities in smoke-exposed lungs using PUBMED searches. We generated hypotheses on the mechanisms by which CC16 limits COPD development, and discuss its potential as a new therapeutic approach for COPD. Expert Opinion CC16 plasma and lung levels are reduced in smokers without airflow obstruction and COPD patients. In COPD patients, airway CC16 expression is inversely correlated with severity of airflow obstruction. CC16 deficiency increases smoke-induced lung pathologies in mice by its effects on epithelial cells, leukocytes, and fibroblasts. Experimental augmentation of CC16 levels using recombinant CC16 in cell culture systems, plasmid and adenoviral-mediated over-expression of CC16 in epithelial cells or smoke-exposed murine airways reduces inflammation and cellular injury. Additional studies are necessary to assess the efficacy of therapies aimed at restoring airway CC16 levels as a new disease-modifying therapy for COPD patients.

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Antiflammin-1 attenuates bleomycin-induced pulmonary fibrosis in mice

Cited by 48 publications

References 36 publications

Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice

Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice

Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle inducing a higher fibrotic response via TGF-β signaling

Club Cell Protein 16 (CC16) Augmentation: A Potential Disease-modifying Approach for Chronic Obstructive Pulmonary Disease (COPD)

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