Oxidative stress in lung epithelial cells from patients with idiopathic interstitial pneumonias

Kuwano, Kazuyoshi; Nakashima, Naotoshi; Inoshima, Ichiro; Hagimoto, Naoki; Fujita, Masaki; Yoshimi, Michihiro; Maeyama, Takashige; Hamada, Naoki; Watanabe, Kentaro; Hara, Nobuyuki

doi:10.1183/09031936.03.00063203

Cited by 113 publications

(86 citation statements)

References 31 publications

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“…26 Our study confirmed this observation, documenting that AGE and RAGE are coexpressed not only in inflammatory cells but also in reactive epithelial cells and fibroblasts in usual interstitial pneumonia and in several inflammatory and fibrosing pulmonary conditions, and that RAGE ligands of the S100-calgranulin family are synchronously present in different inflammatory cell populations. The production of AGE-modified proteins as a consequence of the oxidative stress associated both with pulmonary inflammation and with usual interstitial pneumonia 21,22,27,28 and their binding with RAGE on different cell types can be considered as a possible, as yet not investigated, mechanism of cellular activation that leads to pulmonary tissue damage and fibrosis. In accordance with this hypothesis, NfkB, one downstream product of RAGE-mediated cellular activation, has been shown to have a specific binding site on the promoter of TGF-b1, 29 which is considered one of the key mediators in pulmonary fibrosis.…”

Section: Discussionmentioning

confidence: 99%

The receptor for advanced glycation end products and its ligands: a new inflammatory pathway in lung disease?

et al. 2006

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The binding of the receptor for advanced glycation end products (RAGE) with its ligands begins a sustained period of cellular activation and inflammatory signal amplification in different tissues and diseases. This binding could represent an as yet uninvestigated pathway of inflammatory reaction in the lung, where the presence of the receptor has been largely documented and advanced glycation end products (AGEs) are produced by nonenzymatic glycation and oxidation of proteins and lipids, driven by smoke and pollutants exposure or inflammatory stress. We immunohistochemically assessed the expression of RAGE and of its major proinflammatory ligands, N-e-carboxy-methyl-lysine, S100B and S-100A12 in normal lung and in nonneoplastic lung disorders including smoke-related airway disease, granulomatous inflammation, postobstructive damage and usual interstitial pneumonia. In normal lung low expression of the receptor was observed in bronchiolar epithelia, type II pneumocytes, macrophages and some endothelia. S100A12 and S100B were expressed, respectively, in granulocytes and in dendritic cells. Carboxy-methyl-lysine was present in bronchiolar epithelia and macrophages. In all pathological conditions associated with inflammation and lung damage overexpression of both the receptor and of AGEs was observed in bronchiolar epithelia, type II alveolar pneumocytes, alveolar macrophages and endothelia. RAGE overexpression was more evident in epithelia associated with inflammatory cell aggregates. Fibroblasts in usual interstitial pneumonia expressed both the receptor and AGEs. The number of S100A12 and S100B immunoreactive inflammatory cells was variable. S100A12 was also expressed in mononuclear inflammatory cells and in activated epithelia. The activation of the inflammatory pathway controlled by the RAGE is not specific of a single lung disease, however, it may be relevant as a nonspecific pathway of sustained inflammation in lung tissue, and on this basis therapeutic approaches based on receptor blockage can be envisaged.

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Section: Discussionmentioning

confidence: 99%

The receptor for advanced glycation end products and its ligands: a new inflammatory pathway in lung disease?

et al. 2006

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“…High levels of myeloperoxidase associated with epithelial injury were found in the alveolar epithelial lining fluid (ELF) and BAL fluid (BALF) of patients with IPF [3]. Oxidative modification of mitochondrial DNA has been observed in lung epithelial cells of IPF patients [5]. Oxidised BALF proteins, characterised by oxidation of methionine residues or carbonylation, are increased in patients with IPF [6,7].…”

mentioning

confidence: 95%

Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis

Dalavanga²,

Poulakis³

et al. 2008

European Respiratory Journal

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Haem oxygenase (HO)-1 is an oxidative stress responsive protein that may be involved in the pathogenesis of interstitial lung disease.HO-1 expression in alveolar macrophages from bronchoalveolar lavage was investigated in 24 patients with idiopathic pulmonary fibrosis (IPF), 16 with sarcoidosis, 14 with hypersensitivity pneumonitis (HP) and 13 controls. Using immunocytochemistry, HO-1 expression in macrophages was scored semiquantitatively from 0-3 according to increasing intensity. The mean score of 100 macrophages was calculated. Macrophages were cultured and levels of interleukin (IL)-12 and IL-18 in the culture supernatants were measured by ELISA.The mean score of HO-1 was significantly lower in IPF (67) than in sarcoidosis (105), HP (106) or controls (106). There was no significant difference between sarcoidosis, HP and controls. The score of HO-1 correlated positively with the lymphocyte percentage in sarcoidosis and HP. Positive correlations were found between the score of HO-1 and the release of IL-12 and IL-18 by macrophages in IPF.The expression of haem oxygenase-1, a critical defender against oxidative stress, is decreased in macrophages of idiopathic pulmonary fibrosis patients compared with those with granulomatous lung disorders. This supports the hypothesis of an oxidant-antioxidant imbalance in the pathogenesis of idiopathic pulmonary fibrosis.

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“…The pathogenesis of COPD involves aberrant inflammatory and dysregulated cellular responses of the lung to cigarette smoke (CS) exposure. In lung epithelial cells, cytotoxic exposure to CS reduces Lung-specific isoform (7) required for maximal airway responsiveness (7) mROS Cell death Increased in COPD patients (22,23) Subunit IV increased in the lung epithelial cells from patients with idiopathic interstitial pneumonias (145) COX4i2 may be important in the pathogenesis of asthma (7) Absence of COX4i2 results in lung pathology that worsens over time with impaired airway constriction and reduced airway responsiveness (7) Reduction in bronchial epithelium in asthma (30) Increased by LPS (146 Mitochondrial fusion is mediated by the dynamin-related GTPases mitofusin 1 and 2 (MFN1/2) at the outer mitochondrial membrane (OMM) and by the dynamin-related protein optic atrophy 1 (OPA1) at the inner mitochondrial membrane (IMM). Mitochondrial fission requires the recruitment of dynamin-related protein 1 (DRP1) from the cytosol to receptors (mitochondrial fission protein 1 [FIS1], mitochondrial fission factor [MFF], and mitochondrial elongation factors 1 and 2 [MID51 and MID49]) (ref.…”

Section: Bioenergetics and Nutrient Sensingmentioning

confidence: 99%

Mitochondria in lung disease

Cloonan¹,

Choi²

2016

Journal of Clinical Investigation

224

192

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Oxidative stress in lung epithelial cells from patients with idiopathic interstitial pneumonias

Cited by 113 publications

References 31 publications

The receptor for advanced glycation end products and its ligands: a new inflammatory pathway in lung disease?

The receptor for advanced glycation end products and its ligands: a new inflammatory pathway in lung disease?

Decreased expression of haem oxygenase-1 by alveolar macrophages in idiopathic pulmonary fibrosis

Mitochondria in lung disease

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