• International Journal of Stem Cells
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• 제16권2호
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.

• Tuberculosis and Respiratory Diseases
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• 제61권2호
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• pp.184-188
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• 2006

경피적 척추성형술은 PMMA를 붕괴된 척추체에 경피적으로 주사하여 통증을 완화시키고 척추체를 구조적으로 보강하는 시술이다. 척추성형술은 아주 효과적인 치료방법이기는 하나 합병증이 전혀 없지는 않다. 척추성형술의 많은 합병증은 주로 PMMA 누출과 관련되어 있다. 대부분의 누출은 증상이 없고 또한 폐색전증은 매우 드물지만 시술도중 PMMA의 혈관내 이동을 조기에 발견하지 못할 때 발생할 수 있다. 저자들은 천식으로 인한 기침으로 내원한 환자의 흉부X선에서 우연히 PMMA에 의한 폐색전증을 진단하였기에 문헌 고찰과 함께 보고하는 바이다.

• Tuberculosis and Respiratory Diseases
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• 제43권6호
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• pp.1035-1041
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• 1996

저자등은 Klinefelter 증후군에 병발된 원발성 종격동 혼합형 생식세포종(mixded germ cell tumor)을 가진 환자 1예를 경험하였기에 이에 문헌고찰과 함께 보고하는 바이다.

• Tuberculosis and Respiratory Diseases
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• 제51권3호
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• pp.211-223
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• 2001

연구배경 : 기관지에 리노 바이러스(rhinovirus) 감염은 기관지혈관 내피세포의 투과성을 증가시켜 저비중리포단백(LDL) 같은 혈장단백의 유입을 초래한다. 그런데 산화 저비중리포단백(oxidized LDL)은 단핵세포 대식식세포에서 IL-1, GM-CSF 분비를 유발하고 화학주성과 또한 CD11b/CD18 intergrin을 증가시키며 L-selectin 표현을 감소시킨다. 이러한 소견들은 산화 저비중리포단백이 proimflammatory 효과를 가진다는 것을 시사한다. 연구자들은 산화 저비중리포단백이 리노바이러스 감염시 기도에 과립구를 동원할것이라는 가설하에 산화 저비중리포단백에 의한 호중구와 호산구의 화학주성과 내피세포이동(transendothelial migration)에 대하여 연구하였다. 방 법 : 저비중리포단백을 20-24시간 동안 5mM $CU_2SO_4$로 산화 시키고 conjugated diens 형성 방법으로 234nm에서 산화 정도를 확인하였다. 과립세포들의 화학주성측정은 $3-5{\times}10_5$ 세포들을 transwell 필터에 놓고 $37^{\circ}C$, 5% $CO_2$ 1시간 항온배양후 이동한 세포들을 혈구계로 계산하였다. 과립세포들의 내피세포이동은 인체 미세폐혈관 내피세포(human pulmonary microvascular endothelial cell) 들을 transwell 필터에 배양후 호산구와 호중구를 화학주성물질과 함께 놓은 후 3시간 항온 배양후 이동한 세포들을 혈구계로 계산하였다. 결 과 : 산화 저비중리포단백은 호산구와 호중구에 화학주성이있고 화학주성정도는 저비중리포단백의 농도와 산화 정도에 비례하였다. 또한 산화 저비중리포단백은 과립구의 인체 미세폐혈관 내피세포이동을 농도에 비례히여 자극하였고 호중구가 호산구보다 낮은 농도의 산화 저비중리포단백에 예민하게 반응하였다. 결 론 : 리노바이러스 감염으로 혈관투과정 증가로 저비중리포단백의 유입과 산화를 유발하고 이 산화 저비중리포단백이 기관지 간질세포에 호중구와 호산구이동을 유발하는 한 기전이며 또한 이과립구들이 산화 저비중단백과 함께 기도 염증을 초래할 것으로 사료된다.

• BMB Reports
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• 제55권2호
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• pp.87-91
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• 2022

Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells.

• Molecules and Cells
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• 제39권12호
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• pp.898-908
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• 2016

Despite recent groundbreaking advances in multiple myeloma (MM) treatment, most MM patients ultimately experience relapse, and the relapse biology is not entirely understood. To define altered gene expression in MM relapse, gene expression profiles were examined and compared among 16 MM patients grouped by 12 months progression-free survival (PFS) after autologous stem cell transplantation. To maximize the difference between prognostic groups, patients at each end of the PFS spectrum (the four with the shortest PFS and four with the longest PFS) were chosen for additional analyses. We discovered that integrin-${\alpha}8$ (ITGA8) is highly expressed in MM patients with early relapse. The integrin family is well known to be involved in MM progression; however, the role of integrin-${\alpha}8$ is largely unknown. We functionally overexpressed integrin-${\alpha}8$ in MM cell lines, and surprisingly, stemness features including $HIF1{\alpha}$, VEGF, OCT4, and Nanog, as well as epithelial mesenchymal transition (EMT)-related phenotypes, including N-cadherin, Slug, Snail and CXCR4, were induced. These, consequently, enhanced migration and invasion abilities, which are crucial to MM pathogenesis. Moreover, the gain of integrin-${\alpha}8$ expression mediated drug resistance against melphalan and bortezomib, which are the main therapeutic agents in MM. The cBioPortal genomic database revealed that ITGA8 have significant tendency to co-occur with PDGFRA and PDGFRB and their mRNA expression were up-regulated in ITGA8 overexpressed MM cells. In summary, integrin-${\alpha}8$, which was up-regulated in MM of early relapse, mediates EMT-like phenotype, enhancing migration and invasion; therefore, it could serve as a potential marker of MM relapse and be a new therapeutic target.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.218-226
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• 2015

Background: Eph receptors and ephrin ligands have several functions including angiogenesis, cell migration, axon guidance, fluid homeostasis, oncogenesis, inflammation and injury repair. The EphA2 receptor potentially mediates the regulation of vascular permeability and inflammation in response to lung injury. Methods: Mice were divided into 3 experimental groups to study the role of EphA2 signaling in the lipopolysaccharide (LPS)-induced lung injury model i.e., IgG+phosphate-buffered saline (PBS) group (IgG instillation before PBS exposure), IgG+LPS group (IgG instillation before LPS exposure) and EphA2 monoclonal antibody (mAb)+LPS group (EphA2 mAb pretreatment before LPS exposure). Results: EphA2 and ephrinA1 were upregulated in LPS-induced lung injury. The lung injury score of the EphA2 mAb+LPS group was lower than that of the IgG+LPS group ($4.30{\pm}2.93$ vs. $11.45{\pm}1.20$, respectively; p=0.004). Cell counts (EphA2 mAb+LPS: $11.33{\times}10^4{\pm}8.84{\times}10^4$ vs. IgG+LPS: $208.0{\times}10^4{\pm}122.6{\times}10^4$; p=0.018) and total protein concentrations (EphA2 mAb+LPS: $0.52{\pm}0.41mg/mL$ vs. IgG+LPS: $1.38{\pm}1.08mg/mL$; p=0.192) were decreased in EphA2 mAb+LPS group, as compared to the IgG+LPS group. In addition, EphA2 antagonism reduced the expression of phospho-p85, phosphoinositide 3-kinase $110{\gamma}$, phospho-Akt, nuclear factor ${\kappa}B$, and proinflammatory cytokines. Conclusion: This results of the study indicated a role for EphA2-ephrinA1 signaling in the pathogenesis of LPS-induced lung injury. Furthermore, EphA2 antagonism inhibits the phosphoinositide 3-kinase-Akt pathway and attenuates inflammation.

• 대한한방성인병학회지
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• 제10권1호
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• pp.1-20
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• 2005

Background and Objective: The importance of the presence of eosinophils in the airways of patients with fetal asthma has long been recognized, but the mechanism by which these cells are recruited and retained in the lung are only now being elucidated. Eotaxin is a potent and specific eosinophil chemoattractant that is mobilized in the respiratory epithelium after allergic stimulation. Material and Methods: We used water extracts of Liripois Tuber and pulmonary epithelial cell lines A549(human typeII-like epithelial cells) and human eosinophils. We estimated cytotoxic effects of Liripois Tuber via MTS assay, and estimated the effects of Liripois Tuber on chemokines from prestimulated A549 cells by sandwich ELISA and RT-PCR. We conducted chemotaxis assay on prestimulated eosinophils treated with Liripois Tuber. Result: In this study we demonstrated that $TNF-{\alpha}$, IL-4 and $IL-1{\beta}$ induced the accumulation of chemokines mRNA in the pulmonary epithelial cell lines A549 in dose-dependent manner. Chemokines were inhibited by Liripois Tuber in dose-dependent manner. The eosinophil migration was inhibited at high concentration of Liripois Tuber. Conculusion: These findings indicate that the supression of the expression of chemokines can be accomplished by Liripois Tuber treatment, raising the possibility that Liripois Tuber might be of therapeutic value in diseases such as asthma.

• 대한한방내과학회지
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• 제34권4호
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• pp.362-374
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• 2013

Objectives : This study was carried out to investigate the inhibitory effect of Banhasasim-tang on early reflux esophagitis by control of gastric peristalsis and the lower esophageal sphincter in mice. Methods : Experimental mice were classified into three groups. The normal group were mice with no inflammation. The control group were mice with gastroesophageal reflux elicited by alcohol. The sample group were mice administered Banhasasim-tang after gastroesophageal reflux elicitation. We observed morphological change and production of ghrelin, substance P, and inducible nitric oxide synthase (iNOS) in gastroesophageal junction mucosa. In addition, we examined change of epithelial junction in esophageal mucosa and change of lower esophageal sphincter distribution. Results : The migration of inflammation-related cells in lamina propria of gastroesophageal junction decreased more in the sample group than in the control group. The positive reaction of ghrelin, substance P, and iNOS significantly decreased more in the sample group than in the control group (p<0.05). Injury of the epithelial junction in the esophageal mucosa and outer oblique layer in the lower esophageal sphincter were significantly mitigated by Banhasasim-tang administration in the sample group (p<0.05). Conclusions : According to the above results, it is supposed that Banhasasim-tang inhibits early reflux esophagitis by controlling not only gastric peristalsis and acid secretion through ghrelin, and substance P but also the lower esophageal sphincter through iNOS.

• 대한핵의학회지
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• 제24권2호
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• pp.279-285
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• 1990

Simultaneous presence of ascites and pleural effusion has been documented in patients with cirrhosis of the liver, renal disease, Meigs' syndrome and in patients undergoing peritoneal dialysis. Mechanisms proposed in the formation of pleural effusion in most of the above diseases are lymphatic drainage and diaphragmatic defect. But sometimes, hepatic hydrothoraxes in the absence of clinical ascites and pleural effusion secondary to pulmonary or cardiac disease are noted. It is not always possible to differentiate between pleural effusion caused by transdiaphragmatic migration of ascites and by other causes based soly on biochemical analysis. Authors performed radionuclide scintigraphy after intraperitoneal administration of $^{99m}Tc-labeled$ colloid in 23 patients with both ascites and pleural effusion in order to discriminate causative mechanisms responsible for pleural effusion. Scintigraphy demonstrated the transdiaphragmatic flow of fluid from the peritoneum to pleural cavities in 13 patients correctly. In contrast, in 5 patients with pleural effusion secondary to pulmonary, pleural and cardiac diseases, radiotracers fail to traverse the diaphragm and localize in the pleural space. Ascites draining to mediastinal lymph nodes and blocked passage of lymphatic drainage were also clarified, additionaly. Conclusively, radionuclide peritoneal scintigraphy is an accurate, rapid and easy diagnostic tool in patients with both ascites and pleural effusion. It enables the causes of pleural effusion to be elucidated, as well as providing valuable information required when determining the appropriate therapy.