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1.
Exp Ther Med ; 27(5): 224, 2024 May.
Article in English | MEDLINE | ID: mdl-38596656

ABSTRACT

Yellow nail syndrome (YNS) can induce bilateral exudative pleural effusion; however, to the best of our knowledge, no standard treatment for YNS has been established. The present study describes a patient with YNS for whom the pleural effusion was controlled by prednisolone. A 73-year-old man was referred to the University of Tsukuba Hospital (Ibaraki, Japan) complaining of shortness of breath, which was diagnosed as being due to bilateral pleural effusion. Based on the presence of yellowing and growth retardation of the toenails, lymphedema, bilateral exudative pleural fluid of unknown etiology, and lymphatic congestion on lymphoscintigraphy, the patient was diagnosed with YNS. The pleural fluid was predominantly lymphocytic and responded to systemic steroid administration [prednisolone 30 mg/day (0.5 mg/kg) for 2 weeks, with subsequent weekly tapering]. The general condition of the patient and their dyspnea also improved with treatment. These findings indicated that systemic steroid administration should be considered as one of the treatment options for patients with YNS who are reluctant to undergo chest drainage or pleurodesis due to the potential for a decrease in their ability to perform daily activities and respiratory function.

2.
J Immunol ; 192(3): 958-68, 2014 Feb 01.
Article in English | MEDLINE | ID: mdl-24367027

ABSTRACT

Cigarette smoke (CS)-induced cellular senescence has been implicated in the pathogenesis of chronic obstructive pulmonary disease, and SIRT6, a histone deacetylase, antagonizes this senescence, presumably through the attenuation of insulin-like growth factor (IGF)-Akt signaling. Autophagy controls cellular senescence by eliminating damaged cellular components and is negatively regulated by IGF-Akt signaling through the mammalian target of rapamycin (mTOR). SIRT1, a representative sirtuin family, has been demonstrated to activate autophagy, but a role for SIRT6 in autophagy activation has not been shown. Therefore, we sought to investigate the regulatory role for SIRT6 in autophagy activation during CS-induced cellular senescence. SIRT6 expression levels were modulated by cDNA and small interfering RNA transfection in human bronchial epithelial cells (HBECs). Senescence-associated ß-galactosidase staining and Western blotting of p21 were performed to evaluate senescence. We demonstrated that SIRT6 expression levels were decreased in lung homogenates from chronic obstructive pulmonary disease patients, and SIRT6 expression levels correlated significantly with the percentage of forced expiratory volume in 1 s/forced vital capacity. CS extract (CSE) suppressed SIRT6 expression in HBECs. CSE-induced HBEC senescence was inhibited by SIRT6 overexpression, whereas SIRT6 knockdown and mutant SIRT6 (H133Y) without histone deacetylase activity enhanced HBEC senescence. SIRT6 overexpression induced autophagy via attenuation of IGF-Akt-mTOR signaling. Conversely, SIRT6 knockdown and overexpression of a mutant SIRT6 (H133Y) inhibited autophagy. Autophagy inhibition by knockdown of ATG5 and LC3B attenuated the antisenescent effect of SIRT6 overexpression. These results suggest that SIRT6 is involved in CSE-induced HBEC senescence via autophagy regulation, which can be attributed to attenuation of IGF-Akt-mTOR signaling.


Subject(s)
Autophagy/physiology , Bronchi/pathology , Cellular Senescence/physiology , Epithelial Cells/pathology , Insulin-Like Growth Factor I/physiology , Pulmonary Disease, Chronic Obstructive/pathology , Sirtuins/physiology , Smoke/adverse effects , Acetylation , Autophagy-Related Protein 5 , Cells, Cultured , Cellular Senescence/drug effects , Epithelial Cells/metabolism , Forced Expiratory Volume , Gene Expression Regulation/drug effects , Humans , Microtubule-Associated Proteins/physiology , Mutation , Protein Processing, Post-Translational , Proto-Oncogene Proteins c-akt/physiology , Pulmonary Disease, Chronic Obstructive/physiopathology , RNA Interference , RNA, Small Interfering/pharmacology , Signal Transduction/physiology , Sirtuins/antagonists & inhibitors , Sirtuins/genetics , TOR Serine-Threonine Kinases/physiology , Nicotiana , Vital Capacity
3.
Respir Res ; 14: 30, 2013 Mar 05.
Article in English | MEDLINE | ID: mdl-23497247

ABSTRACT

BACKGROUND: Marked accumulation of alveolar macrophages (AM) conferred by apoptosis resistance has been implicated in pathogenesis of chronic obstructive pulmonary disease (COPD). Apoptosis inhibitor of macrophage (AIM), has been shown to be produced by mature tissue macrophages and AIM demonstrates anti-apoptotic property against multiple apoptosis-inducing stimuli. Accordingly, we attempt to determine if AIM is expressed in AM and whether AIM is involved in the regulation of apoptosis in the setting of cigarette smoke extract (CSE) exposure. METHODS: Immunohistochemical evaluations of AIM were performed. Immunostaining was assessed by counting total and positively staining AM numbers in each case (n = 5 in control, n = 5 in non-COPD smoker, n = 5 in COPD). AM were isolated from bronchoalveolar lavage fluid (BALF). The changes of AIM expression levels in response to CSE exposure in AM were evaluated. Knock-down of anti-apoptotic Bcl-xL was mediated by siRNA transfection. U937 monocyte-macrophage cell line was used to explore the anti-apoptotic properties of AIM. RESULTS: The numbers of AM and AIM-positive AM were significantly increased in COPD lungs. AIM expression was demonstrated at both mRNA and protein levels in isolated AM, which was enhanced in response to CSE exposure. AIM significantly increased Bcl-xL expression levels in AM and Bcl-xL was involved in a part of anti-apoptotic mechanisms of AIM in U937 cells in the setting of CSE exposure. CONCLUSIONS: These results suggest that AIM expression in association with cigarette smoking may be involved in accumulation of AM in COPD.


Subject(s)
Apoptosis Regulatory Proteins/biosynthesis , Gene Expression Regulation , Macrophages, Alveolar/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Aged , Antigens, CD/biosynthesis , Antigens, CD/genetics , Antigens, Differentiation, T-Lymphocyte/biosynthesis , Antigens, Differentiation, T-Lymphocyte/genetics , Apoptosis Regulatory Proteins/genetics , Bronchoalveolar Lavage Fluid , Cells, Cultured , Female , HEK293 Cells , Humans , Lectins, C-Type/biosynthesis , Lectins, C-Type/genetics , Macrophages, Alveolar/pathology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/genetics , Pulmonary Disease, Chronic Obstructive/pathology , U937 Cells
4.
Am J Physiol Lung Cell Mol Physiol ; 304(1): L56-69, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23087019

ABSTRACT

Autophagy, a process that helps maintain homeostatic balance between the synthesis, degradation, and recycling of organelles and proteins to meet metabolic demands, plays an important regulatory role in cellular senescence and differentiation. Here we examine the regulatory role of autophagy in idiopathic pulmonary fibrosis (IPF) pathogenesis. We test the hypothesis that epithelial cell senescence and myofibroblast differentiation are consequences of insufficient autophagy. Using biochemical evaluation of in vitro models, we find that autophagy inhibition is sufficient to induce acceleration of epithelial cell senescence and myofibroblast differentiation in lung fibroblasts. Immunohistochemical evaluation of human IPF biospecimens reveals that epithelial cells show increased cellular senescence, and both overlaying epithelial cells and fibroblasts in fibroblastic foci (FF) express both ubiquitinated proteins and p62. These findings suggest that insufficient autophagy is an underlying mechanism of both accelerated cellular senescence and myofibroblast differentiation in a cell-type-specific manner and is a promising clue for understanding the pathogenesis of IPF.


Subject(s)
Autophagy , Idiopathic Pulmonary Fibrosis/physiopathology , Adaptor Proteins, Signal Transducing/biosynthesis , Cell Differentiation/physiology , Cellular Senescence/physiology , Endoplasmic Reticulum Stress/physiology , Epithelial Cells/pathology , Epithelial Cells/physiology , Humans , Myofibroblasts/cytology , Sequestosome-1 Protein , Tunicamycin/pharmacology , Ubiquitin/biosynthesis
5.
Intern Med ; 51(22): 3155-8, 2012.
Article in English | MEDLINE | ID: mdl-23154723

ABSTRACT

We present a case of organizing pneumonia complicated by pneumothorax in association with cyst formation that developed during corticosteroid treatment. Although it has been reported that the check-valve mechanism is a plausible cause of cyst and pneumothorax formation in patients with organizing pneumonia, the details of the corresponding pathological changes that occur in air-trapping have not been elucidated. A pathological examination of lung specimens obtained with video-assisted thoracoscopic surgery suggested that granulation tissues plugging the bronchiole lumens might be a potential cause of the check-valve mechanism in this case. In this report, we also reviewed eight other cases of organizing pneumonia with pneumothorax or cyst formation.


Subject(s)
Cysts/etiology , Lung Diseases/etiology , Pneumonia/complications , Pneumothorax/etiology , Adrenal Cortex Hormones/adverse effects , Adult , Cysts/diagnosis , Humans , Lung Diseases/diagnosis , Male , Pneumonia/diagnosis , Pneumonia/drug therapy , Pneumothorax/diagnosis , Pneumothorax/surgery , Thoracic Surgery, Video-Assisted , Tomography, X-Ray Computed
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