• 대한한방소아과학회지
• /
• 제23권3호
• /
• pp.233-240
• /
• 2009

Objectives To evaluate that Okwada affected which factors for treatment of lung fibrosis. Methods Bleomycin induced lung fibrosis model made in mice. After Okwada lyophilized, power sample obtained and melt in distilled water. Okwada solution administered mice through oral route on 21 days after bleomycin instillation and this procedure performed once a day for 7 days. We divided by three groups; normal (control), bleomycin induced lung fibrosis without treatment (experimental), bleomycin induced lung fibrosis with treatment (treatment). On six weeks after bleomycin instillation, mice sacrificed and removed lung. Weperformed Western blot analysis for TGF-beta, phosphodiesterase 5A, interleukin (4,5,13) and compared therapeutic effects of Okwada. Results On western blot analysis, all normal and experimental mice detected TGF-beta, phosphodiesterase 5A, interleukin 4,5,13. The amount of band of TGF-beta, phosphodiesterase 5A, interleukin 5 in experimental and treatment group was similar. However, interleukin 4,13 of treatment group decreased compared with experimental group. Conclusions Okwada would be effected the lung fibrosis through suppression of interleukin 4,13.

• Biomolecules & Therapeutics
• /
• 제27권3호
• /
• pp.318-326
• /
• 2019

Sphingosine 1-phosphate (S1P) levels are often found to be elevated in serum, bronchoalveolar lavage, and lung tissue of idiopathic pulmonary fibrosis patients and experimental mouse models. Although the roles of sphingosine kinase 1 and S1P receptors have been implicated in fibrosis, the underlying mechanism of fibrosis via Sphingosine 1-phosphate receptor 2 ($S1P_2$) has not been fully investigated. Therefore, in this study, the roles of $S1P_2$ in lung inflammation and fibrosis was investigated by means of a bleomycin-induced lung fibrosis model and lung epithelial cells. Bleomycin was found to induce lung inflammation on day 7 and fibrosis on day 28 of treatment. On the $7^{th}$ day after bleomycin administration, $S1P_2$ deficient mice exhibited significantly less pulmonary inflammation, including cell infiltration and pro-inflammatory cytokine induction, than the wild type mice. On the $28^{th}$ day after bleomycin treatment, severe inflammation and fibrosis were observed in lung tissues from wild type mice, while lung tissues from $S1P_2$ deficient mice showed less inflammation and fibrosis. Increase in TGF-${\beta}1$-induced extracellular matrix accumulation and epithelial-mesenchymal transition were inhibited by JTE-013, a $S1P_2$ antagonist, in A549 lung epithelial cells. Taken together, pro-inflammatory and pro-fibrotic functions of $S1P_2$ were elucidated using a bleomycin-induced fibrosis model. Notably, $S1P_2$ was found to mediate epithelial-mesenchymal transition in fibrotic responses. Therefore, the results of this study indicate that $S1P_2$ could be a promising therapeutic target for the treatment of pulmonary fibrosis.

• 대한한방내과학회지
• /
• 제25권1호
• /
• pp.71-80
• /
• 2004

Objective : Idiopathic Lung Fibrosis(IPF) is chronic fibrotic interstitial pneumonia. The pathogenesis is unclear. Lonicerae Flos is known to prevent the inflammation and reinforce the immune system. The effects of Lonicerae Flos on bleomycin-induced lung fibrosis is evaluated. Material and Methods: Lonicerae Flos extract was given to the Normal rats, control(bleomycin) rats everyday and treated(bleomycin and lonicerae flos) rats 21.0 mg per body weight 109 for 14 days. 14 days after, we observed the change of leukocyte count and percentage of IFN-gamma and IL-4 in BALF. and that of Semiquantative histological index(SHI). Results : Compared to control rats, Lonicerae Flos decreased leukocyte count(P<0.01) lymphocyte, neutrophil percentage(P<0.05), SHI(P<0.01), IFN-gamma and IL-4(P<0.05) in Treated rats. Otherwise, macrophage percentage was increased(P<0.01) in Treated rats. Conclusion : This study showed that Lonicerae Flos reduced the change of inflammatory cells and cytokines in bleomycin-induced lung fibrosis and reduced the fibrosis of tissue. And, we needed many other distinct researches on lung fibrosis.

• 대한한의학회지
• /
• 제25권2호
• /
• pp.41-50
• /
• 2004

Backgrounds & Objectives: Many acute and chronic lung disorders with variable degrees of pulmonary inflammation and fibrosis are collectively referred to as interstitial lung diseases. Idiopathic pulmonary fibrosis (IPF) is one of several idiopathic interstitial pneumonias with the pathogenesis unclear. Astragali Radix is known to inhibit the Th2 immune response. The effects of Astragali Radix on bleomycin-induced lung fibrosis were evaluated. Materials and Methods: Astragali Radix extract was daily given to the normal rats, control (bleomycin) and treated (bleomycin and Astragali Radix extract, 24.0 mg/10g body weight) rats for 14 days. After 14 days, we observed the change of total leukocyte count and percentage, IFN-gamma and IL-4 in BALF (Bronchoalveolar lavage fluid), and of semiquantitative histological index (SHI). Results: Compared to the control group, Astragali Radix decreased total leukocyte count (p<0.05), lymphocyte (p<0.05), neutrophil (no significance) percentage, SHI (p<0.05), IFN-gamma and IL-4 (p<0.05). Otherwise, macrophage percentage was increased (p<0.01). Conclusion: This study showed that Astragali Radix reduced the incidence of inflammatory cells and cytokines and prevented the fibrosis of tissue in bleomycin-induced lung fibrosis rats.

• Tuberculosis and Respiratory Diseases
• /
• 제49권4호
• /
• pp.441-452
• /
• 2000

연구배경 : 특발성 폐섬유화증에서는 폐암이 호발하는 것으로 알려져 있다. 그동안 이러한 폐암의 호발은 '반혼암'이라는 개념으로 설명되어 왔고 전통적으로는 조직형 중 선암이 가장 많다고 알려져 있었으나 최근에는 편평상피암이 가장 많다는 보고도 있어 논란이 있었다. 그동안의 대부분 연구에서 대상 환자들은 높은 흡연력을 가진 흡연자들이었으나 이 점을 고려하여 섬유화와 연관된 폐암만을 따로 분리하여 분석한 연구는 없었다. 본 연구에서는 특발성 폐섬유화증에 발생한 폐암 중 "섬유화와 연관된 폐암"과 "섬유화와 무관한 폐암"을 나누어 보고 얼마나 많은 폐암이 섬유화와 연관하여 발생하는가, 그리고 섬유화와 연관된 폐암에서는 어떤 조직형이 가장 흔한가를 알아보고자 하였다. 방법 : 1988년 1월부터 1998년 7월 사이에 서울대학교 병원에서 특발성 폐섬유화증에 병발된 폐암으로 진단 받은 환자들을 대상으로 하여 후향적으로 연구를 하였다. 흡연력, 폐암과 특발성 폐섬유화증의 진단 시기, 폐암의 조직형, 폐암의 위치를 조사하였는데 특히 폐암이 섬유화가 진행된 폐실질에서 발생하였는지 여부를 조사하였다. 특발성 폐섬유화증에서 발생하는 폐암중 섬유화와 직접 관련되어 발생하는 폐암이 얼마나 되는지 평가하고자 폐암의 발생 위치에 섬유화가 동반 되어 있는가에 따라 폐암을 분류하려고 시도하였다. 즉, 흉부 전산화 단층 촬영을 검토하여 폐암이 섬유화 병변이 있는 위치에 발생한 경우를 "섬유화와 연관된 폐암"으로, 섬유화 병변과 무관한 위치에 발생한 폐암을 "섬유화와 무관한 폐암"으로 정의하였다. 특발성 폐섬유화증 환자에서 발생한 폐암의 조직형 빈도를 비교하기 위한 대조군으로 1997년도 한국중앙암등록사업 연례보고서 중 폐암의 조직형 분포를 사용하였다. 결과 : 57명의 환자들(남자 54명, 여자 3명)이 대상이 되었다. 특발성 폐섬유화증으로 추적 관찰 중 폐암을 진단 받은 환자가 11%인 6명이었고 나머지 환자들은 폐암과 특발성 폐섬유화증을 동시에 진단받았다. 94.2%인 49명이 흡연자였고 평균 흡연량 47.1$\pm$21.9갑년으로 높은 흡연율을 보였다. 폐암의 위치와 섬유화와의 연관성에 따라 분류하였을 때 "섬유화와 연관된 폐암"이 42명(80.8%), "섬유화와 무관한 폐암"이 10명(19.2%) 이었으며 섬유화와 무관한 위치에 발생한 폐암은 섬유화 병변으로 인해 발생한 반흔 암이 아닌 흡연 등에 연관된 폐암으로 생각되었다. 폐암의 조직형은 전체적으로는 편평상피암이 가장 많고 한국중앙암등록사업 연례보고서 결과와 차이가 없었으나 섬유화와 연관된 폐암만을 따로 살펴 보았을 때에는 선암이 42.9%로 가장 흔한 조직형이었으며 섬유화와 무관한 폐암과는 조직형의 분포에 유의한 차이가 있었다. 결론 : 특발성 폐섬유화증과 병발된 폐암 환자의 81%는 섬유화가 진행된 부위에 폐암이 발생하여 섬유화와 연관된 폐암 발생이 인정되었으나 19%는 섬유화와 무관하게 흡연 등의 인자에 의해 폐암이 발행한 것으로 판단되었다. 전체적으로는 편평 상피암이 가장 많았으나 섬유화와 연관된 폐암만을 대상으로 하였을 때는 선암이 가장 흔한 조직형이었다.

• 대한한방내과학회지
• /
• 제25권4호
• /
• pp.93-104
• /
• 2004

Objectives : The aim was to identify the inhibitory effects of Liriopis Tuber on bleomycin-induced lung fibrosis by analysing the changes of imflammatory cell cytokines and SHI(Semiquantitative Histological Index), Materials and Methods : In this study fibrosis prone C57BL/6J mice were used. Control group was treated with blomycin(0.06mg/0.1 ml) by IT(intratracheal) instillation which is a popular method of inducing lung fibrosis and sample group took Liriopis Tuber water extract(38.0mg/10g body weight) orally for 14 days after IT instillation of blomycin. We measured the total and differential count of WBC, $IFN-{\gamma}$ & IL-4 in mice BALF and SHI(Semiquantitative Histological Index) from lung tissues of mice. BALF and lung tissues of mice were taken 14 days after IT instillation of blomycin. Results : In sample group total WBC count, proportion of neutrophil, SHI and IL-4 significantly(p<0.05) decreased, proportion of macrophage significantly(p<0.05) increased and proportion of lymphocyte, $IFN-{\gamma}$ did not decrease significantly. Conclusions : This study suggests that Liriopis Tuber has an inhibitory effects of pulmonary fibrosis by attenuation of inflammation and Th2 immune response. To determine whether this herbal medicine contribute to cure and prophylaxis of pulmonary fibrosis, further studies on the role of $IFN-{\gamma}$ relating to fibrosis are required.

• 대한한방소아과학회지
• /
• 제23권3호
• /
• pp.217-231
• /
• 2009

Objectives To evaluate that Okwada affected which factors for treatment of lung fibrosis. Methods Bleomycin induced lung fibrosis model made in mice. After Okwada lyophilized, power sample obtained and melt in distilled water. Okwada solution administered mice through oral route on 21 days after bleomycin instillation and this procedure performed once a day for 7 days. We divided by three groups; normal (control), bleomycin induced lung fibrosis without treatment (experimental), bleomycin induced lung fibrosis with treatment (treatment). On six weeks after bleomycin instillation, mice sacrificed and removed lung. We performed Western blot analysis for TGF-beta, phosphodiesterase 5A, interleukin (4,5,13) and compared therapeutic effects of Okwada. Results On western blot analysis, all normal and experimental mice detected TGF-beta, phosphodiesterase 5A, interleukin 4,5,13. The amount of band of TGF-beta, phosphodiesterase 5A, interleukin 5 in experimental and treatment group was similar. However, interleukin 4,13 of treatment group decreased compared with experimental group. Conclusions Okwada would be effected the lung fibrosis through suppression of interleukin 4,13.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권7호
• /
• pp.2613-2617
• /
• 2015

Radiation induced lung injury has long been considered a treatment limiting factor for patients requiring thoracic radiation. This radiation induced lung injury happens early as well as late. Radiation induced lung injury can occur in two phases viz. early (< 6 months) when it is called radiation pneumonitis and late (>6 months) when it is called radiation induced lung fibrosis. There are multiple factors that can be patient, disease or treatment related that predict the incidence and severity of radiation pneumonitis. Radiation induced damage to the type I pneumocytes is the triggering factor to initiate such reactions. Over the years, radiation therapy has witnessed a paradigm shift in radiation planning and delivery and successfully reduced the incidence of lung injury. Radiation pneumonitis is usually a diagnosis of exclusion. Steroids, ACE inhibitors and pentoxyphylline constitute the cornerstone of therapy. Radiation induced lung fibrosis is another challenging aspect. The pathophysiology of radiation fibrosis includes continuing inflammation and microvascular changes due to pro-angiogenic and profibrogenic stimuli resembling those in adult bronchiectasis. General supportive management, mobilization of airway secretions, anti-inflammatory therapy and management of acute exacerbations remains the treatment option. Radiation induced lung injury is an inevitable accompaniment of thoracic radiation.

• Journal of Yeungnam Medical Science
• /
• 제37권4호
• /
• pp.269-276
• /
• 2020

Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

• 대한한방소아과학회지
• /
• 제22권2호
• /
• pp.37-49
• /
• 2008

Objectives : Idiopathic pulmonary fibrosis (IPF) is chronic fibrotic interstitial pneumonia and the pathogenesis is unknown. Peucedani Radix is well-known for the treatment of respiratory diseases and pulmonary hypertension. This study was to evaluate the effectiveness of Peucedani Radix on the bleomycin-induced lung fibrosis model (BLFM) in mouse. Methods : We induced lung fibrosis by intratracheal instillation of bleomycin in C57BL/6J. We compared two groups BLFM without Peucedani Radix (group I) and BLFM with Peucedani Radix (group II). We performed bronchoalveolar lavages (BAL) and obtained lung specimens from both group I and II on the 7th (A) and 21st (B) day, and also for the normal group. We compared with group I and II to find BAL by using ANOVA test and to find pathologic symptoms by using semiquantitative histological index (SHI). Results : In BAL, total cell counts, lymphocytes, and neutrophils was increased in both group I and II comparing with normal group. However, lymphocyte level was decreased more in group IIB than group IB. It was statistically significant. In microscopic findings, scores of SHI in normal group, group IB and IIB were 0.33, 4.47, and 1.96 each. Conclusions : Peucedani Radix might have inhibitory effect on lung fibrosis by reducing inflammatory cells in bleomycin-induced lung fibrosis model in mouse.