• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.68-68
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• 2002

To investigate the disease and recovery process of pneumoconiosis induced by welding-fume exposure, a lung fibrosis model was established by building a stainless steel arc welding fume generation system and exposing male Sprague-Dawley rats for 90 days.(omitted)

• Tuberculosis and Respiratory Diseases
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• 제75권5호
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• pp.214-217
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• 2013

Treatment of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is difficult because the mortality rate after surgery or chemotherapy is high for these patients. Spontaneous regression of cancer is rare, especially in lung cancer. A 62-year-old man, previously diagnosed with IPF, presented with stage IIIC (T2N3M0) non-small cell lung cancer. About 4 months later, spontaneous regression of the primary tumor was observed without treatment. To the best of our knowledge, this is the first report of spontaneous regression of lung cancer in a patient with IPF.

• Tuberculosis and Respiratory Diseases
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• 제52권5호
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• pp.550-556
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• 2002

Microscopic polyangiitis is a systemic small-vessel vasculitis that is associated primarily with necrotizing glomerulonephritis and pulmonary capillaritis. A recurrent and diffuse alveolar hemorrhage due to pulmonary capillaritis is the main clinical manifestation of lung involvement. Recently, and interstitial lung disease that mimics idiopathic pulmonary fibrosis was reported to be rarely associated with microscopic polyangiitis. Here we report two patients with microscopic polyangiitis who showed a honeycomb lung at the time of the initial diagnosis with a brief review of relevant literature.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.835-845
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• 1998

연구배경: 유리규산(silica)이 폐장내로 흡입되면 폐장내 염증세포의 축적이 발생하고 폐실질과 간질에 섬유화가 발생한다. Silica가 폐장내로 흡입되면 대삭세포에 탐식되어 염증매개물을 분비한다. 대식세포에서 염증반응에 중요하게 관여히는 cytokines은 IL-1$\beta$, IL-6, TNF-$\alpha$ 등이 있으며 후기 섬유화에 관계하는 TGF-$\beta$ 등이 분비되어 폐섬유화의 진행과 유지에 중요한 역할을 한다. 그러나 silica에 의한 폐섬유화 과정에서 각 cytokine의 역할과 분비부위 시간에 따른 변화에 대해서는 아직 확실히 규명된 바 없다. 방 법: silica 투여시 폐섬유화증이 잘 유발되어지는 C57BL/6J(ref) mouse의 폐장내로 silica를 투여 후 1 일, 2 일, 7 일, 2 주, 4주, 8주, 12주째마다 폐장을 적출하여 시간에 따른 폐조직의 변화와 면역화학조직염색법을 이용하여 IL-1$\beta$, IL-6, TNF-$\alpha$, TGF-$\beta$ 단백 발현의 변화와 분비부위를 관찰하였다. 결 과: Silica군에서는 2주부터 육안적 소견의 변화가 관찰되었으며 8주째 변화가 가장 심하였고 초기에 염증세포의 침윤이 기관지와 세기관지 주위로 시작되어 8 주째는 기관지 주위의 심한 염증세포 침윤과 섬유화 결절에 의해서 기관지가 완전히 폐쇄되는 소견을 보였다. IL-6 의 발현은 혈관에서는 변화없이 지속적으로 발현되었고 시간 경과에 따라 기도상피세포와 혈판내피세포에서 IL-6 발현이 관찰되어 IL-6의 형성은 혈관에서 기도내로 이동하는 염증세포에 의해 과형성됨을 알 수 있었다. IL-1는 정상군의 혈관내피세포에서 1도 정도의 경한 발현이 있은 후 큰 변화없이 12주까지 지속적으로 발현되었다. TNF-$\alpha$는 기도상피세포에서 발현이 점차 증가하였고 2주째 기관지 주위에 염증세포의 침윤이 심해지면서 형성된 결절에서 강한 발현이 나타난 후 8주까지 지속되었다. TGF-$\beta$는 기관지 주위에서 초기에 발현을 관찰할 수 없었으나 염증 세포의 침윤이 심해지는 2 주째부터 강한 발현이 나타난 후 12주까지 지속적으로 높은 발현을 나타내었다. 결 론: Silica를 폐장내 투여시 IL-1$\beta$, IL-6, TNF-$\alpha$가 조기에 분비되어 모두 폐섬유화의 염증반응에 관여하고 TGF-$\beta$는 후기의 폐섬유화에 유지에 관여할 것으로 추정되며 silica에 의한 폐섬유화의 조절방법으로는 TNF-$\alpha$의 형성조절이 좋은 방법이 될 수 있을 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제84권4호
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• pp.255-262
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• 2021

Microscopic polyangiitis (MPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated necrotizing vasculitis, which mainly affects small vessels in various organs, especially the lungs. The two key pulmonary manifestations, interstitial lung disease (ILD) and diffuse alveolar hemorrhage (DAH), increase the morbidity and death rate of patients with MPA. ILD is more common in MPA than in other ANCA-associated vasculitis subsets and is primarily associated with myeloperoxidase-ANCA. Unlike alveolar hemorrhage due to pulmonary capillaritis, ILD can initially manifest as isolated pulmonary fibrosis. Of note, its most frequent radiographic pattern is the usual interstitial pneumonia pattern, similar to the characteristic pattern seen in idiopathic pulmonary fibrosis. In this review we present the pathogenesis, clinical manifestations, and radiographic and histopathologic features of ILD and DAH in MPA. We also briefly summarize the outcome and therapeutic options for the two conditions.

• Journal of Chest Surgery
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• 제55권4호
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• pp.357-360
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• 2022

Patients with severe coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) may exhibit pulmonary fibrosis after the viral illness resolves. Some of these patients may experience severe functional lung impairment, and thus require transplants to prevent death or maintain a tolerable quality of life. Considering the reversibility of COVID-19 ARDS, lung transplant candidates are observed for 1-2 months and must be selected very carefully before transplantation. As the short-term outcomes of such patients are comparable to those of patients with other indications for transplantation, lung transplantation should be actively considered.

• Toxicological Research
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• 제24권4호
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• pp.273-280
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• 2008

The single intratracheal instillation (ITI) of bleomycin (BLM) is a widely used method for inducing experimental pulmonary fibrosis in rat model. In the present study, pulmonary function tests (PFTs) of tidal volume ($V_T$), minute volume ($V_M$), and respiratory frequency ($F_R$) have been applied to study their possibility as a tool to monitor the progress of BLM-induced lung injury in rat model. Rats were treated with a single ITI of BLM (2.5 mg/kg) or saline (control). Animals were euthanized at 3, 7, 14, 21, and 28 days post-ITI. Lung toxicity effects were evaluated by inflammatory cell count, lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF), and light microscopic examination of lung injury. The PFT parameters were measured immediately before the animals were sacrificed. BLM treatment induced significant cellular changes in BALF-increase in number of total cells, neutrophils, and lymphocytes along with sustained increase in number of macrophages compared to the controls at days 3, 7, and 14. BALF LDH level was significantly increased compared to that in the controls up to day 14. On day 3, infiltration of neutrophils was observed in the alveolar spaces. These changes developed into marked peribronchiolar and interstitial infiltration by inflammatory cells, and extensive thickening of the interalveolar septa on day 7. At 14, 21, and 28 days, mild peribronchiolar fibrosis was observed along with inflammatory cell infiltration. The results of PFT show significant consistencies compared to the results of other toxicity tests. These data demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days post-ITI of BLM based on the observation of fibrosis at 14, 21, and 28 days. Further, the progress of lung injury can be traced by monitoring the PFT parameters of $F_R$, $V_T$, and $V_M$.

• Toxicological Research
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• 제25권4호
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• pp.217-224
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• 2009

Inhaled inorganic dusts such as coal can cause inflammation and fibrosis in the lung called pneumoconiosis. Chronic inflammatory process in the lung is associated with various cytokines and reactive oxygen species (ROS) formation. Expression of some cytokines mediates inflammation and leads to tissue damage or fibrosis. The aim of the present study was to compare the levels of blood cytokines interleukin (IL)-$1\beta$, IL-6, IL-8, tumor necrosis factor (TNF)-$\alpha$ and monocyte chemoatlractant protein (MCP)-1 among 124 subjects (control 38 and pneumoconiosis patient 86) with category of chest x-ray according to International Labor Organization (ILO) classification. The levels of serum IL-8 (p= 0.003), TNF-$\alpha$ (p=0.026), and MCP-1 (p=0.010) of pneumoconiosis patients were higher than those of subjects with the control. The level of serum IL-8 in the severe group with the small opacity (ILO category II or III) was higher than that of the control (p=0.035). There was significant correlation between the profusion of radiological findings with small opacity and serum levels of IL-$1\beta$(rho=0.218, p<0.05), IL-8 (rho=0.224, p<0.05), TNF-$\alpha$ (rho=0.306, p<0.01), and MCP-1 (rho=0.213, p<0.01). The serum levels of IL-6 and IL-8, however, did not show significant difference between pneumoconiosis patients and the control. There was no significant correlation between serum levels of measured cytokines and other associated variables such as lung function, age, BMI, and exposure period of dusts. Future studies will be required to investigate the cytokine profile that is present in pneumoconiosis patient using lung specific specimens such as bronchoalveolar lavage fluid (BALF), exhaled breath condensate, and lung tissue.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.434-445
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• 2023

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

• Tuberculosis and Respiratory Diseases
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• 제50권2호
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• pp.182-195
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• 2001

연구배경 : IPF에 의한 유병률과 사망률은 점차 증가하는 추세이나 좋은 치료는 없는 상태이다. 폐 섬유화 과정에서 TGF-${\beta}_1$, TNF-$\alpha$, ET-1, IFN-$\gamma$등의 사이토카인이 중요한 역할을 함이 알려져 있다. 본 실험은 파라콰트를 기관지 내로 주입하여 섬유화가 유발되는 과정의 백서의 폐 조직 내에서 ET-1과 TGF-${\beta}_1$의 발현을 살펴보고, 또한 비선택적 ET-1 receptor blocker인 Bosentan이 폐 섬유화의 치료에 효과가 있는지를 보고자 하였다. 방 법 : 웅성 7-8 주령의 백서 120 마리를 세 그룹으로 나누고 제 1그룹은 대조군으로 하여 기관지 내로 생리 식염수를 투여하였고, 제2그룹은 파라콰트를 투여하였으며, 제3그룹은 첫날 파라콰트를 투여한 후 매일 gastric gavage 방법으로 보센탄을 투여하였다. 파라콰트 혹은 생리식염수를 투여한 지 1, 3, 5, 7, 10, 14일째 각각 세 그룹의 일정 수를 희생하여 폐의 병리조직을 보고 면역세포화학염색으로 ET-1과 TGF-${\beta}_1$의 발현 율을 조사하여 분석하였다. 폐 섬유화의 정도는 H&E 염색과 Masson trichrome 염색을 하여 컴퓨터 영상분석을 시행하였고, 면역세포화학염색은 염색정도에 따라 반정량화하여 분석하였다. 결 과 : 파라콰트를 투여한 군이 대조군에 비해 콜라겐의 침착이 실험 3일째부터 현저히 증가하였고, ET-1과 TGF-${\beta}_1$의 발현이 주로 실험 초기에 증가하였다. 그러나 보센탄을 투여한 경우 콜라겐이 침착된 양에는 유의한 변화가 없었고 파라콰트군과 비교해서 ET-1과 TGF-${\beta}_1$의 발현에 뚜렷한 변화는 없었다. 결 론: 파라콰트를 투여한 경우 폐 섬유화가 증가하였다. 그리고 ET-1과 TGF-${\beta}_1$의 발현이 증가하였다. 그러나 ET-1 에 대한 receptor blocker인 보센탄이 폐 섬유화를 막지는 못하였다. 파라콰트에 의한 폐 섬유화에 ET-1이 연관성이 있으나 그 역할에 대해서는 추후 더 연구가 필요할 것으로 사료된다.