Activation of Transient Receptor Potential Melastatin Family Member 8 (TRPM8) Receptors Induces Proinflammatory Cytokine Expressions in Bronchial Epithelial Cells

김주희,Young Sook Jang,Hwan Il Kim,박지영,박성훈,Yong Il Hwang,Seung Hun Jang,Ki-Suck Jung,Hae Sim Park,Choon-Sik Park 대한천식알레르기학회 2020 Allergy, Asthma & Immunology Research Vol.12 No.4

Purpose: Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. Methods: The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. Results: Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. Conclusions: TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

A novel, topical, nonsteroidal, TRPV1 antagonist, PAC-14028 cream improves skin barrier function and exerts anti-inflammatory action through modulating epidermal differentiation markers and suppressing Th2 cytokines in atopic dermatitis

Lee, Ji-Hae,Choi, Chang Soon,Bae, Il-Hong,Choi, Jin Kyu,Park, Young-Ho,Park, Miyoung Elsevier 2018 JOURNAL OF DERMATOLOGICAL SCIENCE Vol.91 No.2

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Although it is established that epidermal barrier disturbance and immune dysfunction resulting in IgE sensitization are critical factors in the development of cutaneous inflammation, the pathogenesis and targeted therapy of atopic dermatitis (AD)-specific pathways have still been unknown.</P> <P><B>Objective</B></P> <P>Taking into account the fact that Th2 cytokines in AD have both unique and overlapping functions including increased epidermal thickening, inflammation, and decreased expressing of the barrier proteins keratinocyte differentiation, we sought to clarify our hypothesis that TRPV1 antagonist plays a critical role in skin barrier function and can be a therapeutic target for AD.</P> <P><B>Methods</B></P> <P>AD-like dermatitis was induced in hairless mice by repeated oxazolone (Ox) challenges to hairless mice. The functional studies concerning skin barrier function, anti-inflammatory action, and molecular mechanism by TRPV1 antagonism were conducted by histopathological assays, ELISA, qPCR, western blotting, and skin blood flow measurement.</P> <P><B>Results</B></P> <P>Topically administered TRPV1 antagonist, PAC-14028 (Asivatrep: C<SUB>21</SUB>H<SUB>22</SUB>F<SUB>5</SUB>N<SUB>3</SUB>O<SUB>3</SUB>S), improved AD-like dermatitis and skin barrier functions, and restored the expression of epidermal differentiation markers. In addition, the PAC-14028 cream significantly inhibited cutaneous inflammation by decreasing the expression of serum IgE, and the epidermal expression of IL-4, and IL-13 in Ox-AD mice. These results may provide a novel insight into the molecular mechanism of PAC-14028 cream involved in anti-inflammatory effects and skin barrier functions by suppressing the multiple signaling pathways including IL-4/-13-mediated activation of JAK/STAT, TRPV1, and neuropeptides.</P> <P><B>Conclusion</B></P> <P>PAC-14028 cream can be a potential therapeutic tool for the treatment of chronic inflammation and disrupted barrier function in patients with AD.</P> <P><B>Highlights</B></P> <P> <UL> <LI> PAC-14028 1% topical cream is an anti-inflammatory, non-steroidal TRPV1 antagonist. </LI> <LI> PAC-14028 cream treatment reduced AD-like symptoms and improved skin barrier functions in Ox-induced <I>in vivo</I> murine model. </LI> <LI> PAC-14028 suppressed the signaling pathways including IL-4/-13 mediated activation of JAK/STAT, TRPV1, and neuropeptides. </LI> </UL> </P>

누에와 육계 복합 추출물의 in vivo 면역증진 기능성 연구

김경조 ( Kyeong Jo Kim ),박해진 ( Hae Jin Park ),김일규 ( Il Gyu Kim ),김민주 ( Min Ju Kim ),신미래 ( Mi-rae Shin ),노성수 ( Seong-soo Roh ) 대한본초학회 2018 大韓本草學會誌 Vol.33 No.4

Objectives : The aim of this study was to investigate the immunopotentiating activity of combine extract that Silkworm and Cinnamomum cassia . Recently, acute epidemic diseases such as cold and viral respiratory diseases have been emerging. So, interested in immunity enhancement has been increasing, and research on natural products to promote immunity activity has been actively conducted. Methods : To confirm the immunopotentiating activity effect, Silkworm (SW), Cinnamomum cassia (CC), and SWCC combined extracts were treated 14 days at 300 ㎎/kg/day. The changes of glutamic oxalacetic transaminase (GOT), glutamic pyruvate transaminase (GPT) in serum were analyzed after experiment. The changes in the total spleen cell number were measured. Immune cells in spleen were analyzed using fluorescence activated cell sorter (FACS). also, analyzed the expression of cytokines in spleen. Results : Total number of cells in the spleen and FACS analysis of T lymphocytes activated in the spleen showed that the SWCC combined treated group had much higher frequency of active cells than both single groups. The ratio of CD4+CD8+, CD4+CD69+ and CD4+CD25+ T cells in spleen, SWCC is higher than other groups except Nor in CD4+, CD4+CD69+, CD4+CD25+ T cells. The results of this study suggest that SWCC can help immune function via IL-2, IL-10, IL-12, IFN-γ cytokine production, increased T lymphocytes and splenocyte proliferation. Conclusion : Therefore, these results suggested that the SWCC combined extracts administration increase stronger immunity enhancement than when SW and CC adminstration.

Graphene–Ionic Liquid Based Hybrid Nanomaterials as Novel Lubricant for Low Friction and Wear

Khare, Varsha,Pham, Minh-Quan,Kumari, Nitee,Yoon, Hae-Sung,Kim, Chung-Soo,Park, Jae-IL,Ahn, Sung-Hoon American Chemical Society 2013 ACS APPLIED MATERIALS & INTERFACES Vol.5 No.10

<P>Hybrid nanomaterials offer potential scope for an increasing number of novel applications when engineered to deliver usefully functional properties. Recent advancements in the design of new material products that result from interactions among different compositions at the nanoscale and microscale has led to innovative ways to fabricate and process hybrids with altered structural physicochemical properties. An example is the development of novel “lubricants” that make use of ionic liquids (ILs) and their ability to induce exploitable molecular assemblies at the IL–graphene interface. In the present study, we report the potential of graphene–IL hybrid nanomaterials for engineering applications with a focus on “lubricant” properties to reduce frictional forces to enhance tribological performance. The present contribution outlines the wear and tribological properties (friction and lubrication) of a highly viscous IL [BMIM][I] and its comparison with its nanohybrid material counterpart. Detailed structural–microstructural investigations of the nanohybrid materials were performed using X-ray diffraction and microscopic techniques employing scanning electron (SEM), transmission electron (TEM), and high resolution transmission electron (HRTEM) microscopies. A comparative study of the morphology of friction track and wear behavior was assessed by SEM and TEM. These characteristic properties within and outside the friction track were further correlated with physical and chemical interactions obtained by contact angle measurements and Raman spectroscopy and energy dispersive analysis by X-ray (EDAX).</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2013/aamick.2013.5.issue-10/am302761c/production/images/medium/am-2012-02761c_0016.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am302761c'>ACS Electronic Supporting Info</A></P>

Mesenchymal Stem Cells Ameliorate Adriamycin Induced Proteinuric Nephropathy

강희경,박소연,하일수,정해일,최용,Kang, Hee-Gyung,Park, So-Yeon,Ha, Il-Soo,Cheong, Hae-Il,Choi, Yong Korean Society of Pediatric Nephrology 2010 Childhood kidney diseases Vol.14 No.1

목 적 : 사구체신염은 흔히 단백뇨를 보이며 특이 치료법이 없고, 만성 신부전으로 발전하는 경우가 많다. 몇몇 연구에서 중간엽 줄기세포(Mesenchymal stem cell, MSC)를 실험적 사구체신염에 투여하여 단백뇨가 호전된 것을 보고한 바 있으나, 이는 신염을 일으키는 약제와 중간엽 줄기세포를 함께 투여하거나 신장에 직접 투여한 것이었다. 본 연구에서는 실험적 신병증에서 단백뇨가 발현된 시점에서 정주 요법으로 MSC를 투여함으로써 MSC의 임상적인 적용 가능성을 탐색하였다. 방 법 : 실험용 생쥐에 Adriamycin을 투여하여 신병증(ADR-GN)을 유발한 후, 2주 후에 대량의 단백뇨를 확인하고 MSC를 생쥐 꼬리의 정맥에 주사하였다. MSC에 의한 질병 완화의 기전을 확인하기 위한 in vitro 실험으로 mixed lymphocyte culture(MLC)에 MSC를 투여하였을 때의 염증 관련 cytokine인 IFN-$\gamma$ and IL-10의 변화를 측정하였다. 결 과 : 실험용 생쥐에 ADR-GN를 유발하고 단백뇨가 보일 때 MSC를 정주한 군에서는 단백뇨의 소실이 더 먼저 관찰되었다. 또한 MSC를 투여받은 군에서의 생존률이 더 나은 경향이 관찰되었다. MLC 에 MSC를 투여하였을 때, 염증을 유발하는 cytokine인 IFN-$\gamma$ 는 감소하고 염증을 억제하는 cytokine인 IL-10는 증가하였다. 결 론 : 이 연구는 이전의 보고들에서 관찰되었던 사구체신염에서의 MSC의 질병완화 효과가 좀더 임상적으로 적용 가능한 방법으로 투여된 경우, 즉 단백뇨가 있을 때 정주 요법으로 투여한 경우에도 관찰됨을 확인하였다. 이러한 효과의 기전과 임상적용에 요구되는 안전성 등에 대한 확인을 위해서는 추가 연구가 필요하겠다. Purpose : Glomerulonephropathy (GN) often manifests as proteinuria and progresses to chronic renal failure without specific therapy. Mesenchymal stem cell (MSC) has been tried as a therapeutic agent in experimental GN, and previous studies showed that administration of MSC concomitantly to the insult inducing GN or via intra-renal administration ameliorated proteinuria. The purpose of this study was to test the therapeutic potential of MSC administered via intravenous route at the time of clinically evident proteinuria. Methods : MSCs were administered intravenously via tail vain into the mice with adriamycin (ADR) induced nephropathy (ADR-GN), two weeks after ADR injection when massive proteinuria was evident. To test the capacity of MSC modulate the cytokine production in the inflammatory milieu, the concentrations of IFN-$\gamma$ and IL-10 were measured in the supernatant of in vitro mixed lymphocyte culture (MLC) with or without additional MSC. Results : MSCs administered intravenously into the proteinuric mice with ADR-GN accelerated the recovery of this experimental GN with disappearance of proteinuria in two weeks when the saline treated (control) mice still showed significant proteinuria. The mice treated with MSC also had a tendency of better survival. Addition of MSC decreased IFN-$\gamma$ and increased IL-10 in the supernatant of MLC. Conclusion : This study showed that MSC had a therapeutic potential even when administered in a more clinically relevant setting into a proteinuric glomerulonephropathy model. Further study to verify the mechanism and long-term safety of this phenomenon is required.

제 2형 당뇨병 환자에서 대사증후군의 유병률 및 관련요인의 특징

박철진,박거운,박일구,신지혜,김진화,배학연,김상용 朝鮮大學校 附設 醫學硏究所 2007 The Medical Journal of Chosun University Vol.32 No.3

Background: People with insulin resistance has a higher risk of developing cardiovascular disease. This leads to the importance in diagnosing metabolic syndrome. The incidence of metabolic syndrome has increased significantly in korea because of an increased population of obese people and also the incidence of DM. There have been many studies done on the incidence of metabolic syndrome in the general population. Therefore, the authors have designed this study to identify the incidence of metabolic syndrome in patients with type 2 DM and also the associated characteristics in that population. Methods: The study included 169 adults over the age of 20 (84 males and 85 females) admitted to the endocrinology department of Chosun University between Jan, 1st 2005 and May, 31st 2006. Out of the people diagnosed with type 2 DM people were excluded when any of the physical measurements (height, weight, blood pressure, abdominal circumference) and blood measurements (TG, HDL-cholesterol, fasting blood sugar) were insufficient and when the patient was taking any drugs other than anti-hy-pertensive agents and oral anti-diabetic agents. Obesity and the other risk factors were defined by the Asian-Pacific guideline and 2001 ATP III of NCEP, respectively. Result: The each prevalence according to the metabolic syndrome criteria of the type 2 DM patients showed low HDL cholesterolemia with the highest incidence of 57.4% followed by hypertng1yceridemia(52.0%), obesity(40.9%) and hypertension(33.0%). The each incidence of diagnostic criteria in metabolic syndrome according to sex was different, In males, hypertriglyceridemia was the highest with the incidence of 57.7% followed by low HDL-cho1estero1emia(49.5%), obesity(40.9%) and hypertension (30.0%). In women, the incidence were low HDL-cho1estero1emia(64.8%), hyperthg1yceridemia(47.6%), obesity(45.0%) and hypertension(36.0%), in a descending order. The analysis between the diagnosis of metabolic syndrome in type 2 DM patients and the criteria showed that hyperthglyceridemia (correlative value 0.575) had the highest correlation followed by low HDL-cholesterolemia (correlative value 0.446), obesity (correlative value 0.350) and hypertension (correlative value 0.410). All the correlations were statistically significant with a p-value less than 0.01. Conclusions: Type 2 DM is a important factor of metabolic syndrome based on insulin resistance. The control of blood glucose with prevention and early diagnosis of the other factors related to metabolic syndrome in type 2 DM is important for preventing cardiovascular complications.

제조업의 경쟁력과 재무성과와의 인과모형에 관한 실증적 분석

박해철,방재일 中央大學校經營硏究所 2002 經營學論集 Vol.28 No.2

대학 교직원의 라이프스타일에 따른 세분시장별 대학 교직원 급식소 서비스 품질 인식 분석

박문경,양일선,김동훈,신서영,이해영 대한지역사회영양학회 2003 대한지역사회영양학회지 Vol.8 No.4

Market segmentation helps providers to find better marketing opportunities and allows foodservice managers to develop the right product for each target market. Therefore, this study, taking university faculty and staff as subject, is intended to diagnose the relative value of service quality attribute, on the basis service quality scenario of faculty foodservice to suggest price for improving customer loyalty in market segments. A questionnaire was developed and mailed to 600 Yonsei university faculty and staffs. A total of 385 questionnaires were usable; resulting in a 58.7% of faculty and a 69.7% of staff response rate, respectively. Statistical data analysis was completed using the SAS/Win 6.12 for descriptive Analysis, ANOVA, principal factor analysis, cluster analysis, reliability test and discriminant analysis. The results of the study are as below. Eighteen questions were selected for measuring respondents' lifestyle by AIO method and the seven lifestyle factors derived from factor analysis and aggregated distinct 4 clusters. Service quality attributes of the scenario were determined with 'food quality', 'menu variety', 'atmosphere', 'fast service', and 'clean and sanitation'. 'food quality', 'menu variety', 'atmosphere', 'fast service', and 'clean and sanitation', in decreasing order, were identified as improving customer loyalty. However, most faculty and staffs were satisfied with the present meal price. The result of this study indicates that the relative value of service quality was differed significantly among the various market segments. 'Food quality', 'menu variety', and 'atmosphere' were determined as major service quality attributes. Thus, customer loyalty could be increased by improving food taste and quality, atmosphere, and service delivery.

재래(흑색) 염소의 비육에 관한 연구 : Ⅰ. 일측 갑상선 제거가 체중, 체온 및 맥박에 미치는 영향 Ⅰ. Effect of Uni-lateral Thyroidectomy on Body Weight, Body Temperature and Pulse Rate

박무현,권해병,양일석 慶尙大學校 1975 論文集 Vol.14 No.-

In order to investigate the relationship of body weight, body temperature and pulse rate to hypothyroidism in the state of uni-lateral thyroidectomy of Korean native goat, a brief observation was carried out. Twenty healthy male adult goats (7 months old) were used in the present experiment dividing into 2 groups, the control with 5 and the experimental with 15, respectively. Individuals of the experimental group were received uni-lateral thyroidectomy by surgical operation, while individuals of the control group, on the other hand, were received sham-operation. Measurements of body weight, body temperature and pulse rate after the operation were performed in duration of 48 days by 2 days interval. The results obtained could be summerized as follows. 1. There were no significant changes in body weight of experimental group compared to that of control group. 2. Uni-laterally thyroidectomized goat showed no changes in body temperature, which is seemed to he doe to a compensatory effect. 3. Statistical calculation did not show any difference in pulse rate between control and experimental group. The present experiment can he concluded that uni-lateral thyroidetomy had not any effect on the changes body weight, body temperature and pulse rate.

갑상선결절의 임상 및 초음차소견의 진단적 가치

박거운,박철진,박일구,신지혜,정중화,배학연,김상용 朝鮮大學校 附設 醫學硏究所 2007 The Medical Journal of Chosun University Vol.32 No.2

Backgrounds: Thyroid nodule have been relatively common disease and it's prevalence estimated about 4-7%. Recently, high resolution ultrasonography has made the detection of small thyroid nodule possible, Increases in the detection of thyroid nodule have created a clinical dilemma on how to properly manage such thyroid nodules. We investigated the prevalence, clinical and ultrasonographic characterristics, and optimal diagnostic approach toward detected benign and malignant thyroid nodules. Methods: A retrosepctive review was undertaken on the 372 patients who was done Ultrasonograpy guided fine needle aspiration biopsy in Chosun University Hospital, Gwang-Ju, Korea between July 2003 and Spring 2005. Devided into four group such as benign and malignant thyroid nodule on the basis of size 1.5Cm. The review consisted of thyroid function test, antithyroid antibodies, thyroid autoantibodies, thyroid ultrasonography, fine needle aspiration biopsy in each group. Results: The prevalence of thyroid nodule malignancy rate was 18.0%. The prevalence of thyroid incidentaloma malignanct rate was 17.5%. There were no significant differences in age, sex, thyroid function test and size between the benign, malignant incidentalomas and nodule. Ultrasonographic characteristics, include ultrasonography index point showed meaningful diagnostic value for the detection of malignancy in thyroid nodule, Conclusion: Thyroid cancers are fairly common finding. There are no clinical difference between benign and malignant thyroid nodule; however, ultrasonographic findings can be used to decision of optimal management strategies 배경: 최근갑상선 초음파의 빈번한 시행으로 갑상선 결절의 발견이 증가하고 있다. 이러한 갑상선 결절중 특히 갑상션우연종을 임상적으로 어떻게 접근하고 치료를해야하는지는 적지 않는 문제가 되고 있다. 본 연구에서는 갑상선 우연종 및 직경 1.5 cm 이상의 갑상션결절의 유병률, 임상적 특징, 초음파특정 및 초음파의 진단적 유용성에 대해 알아 보았다. 방법: 2003년 7윌부터 2005년 3월까지 조선 대학교병원 내과 및 일반외과및 건강검진 센터를 통해 갑상선 초음파, 경동맥 초음파 및 경부 CT등을 통해 우연히 발견된 갑상션결절을 가진 372명을 대상으로 후향적 연구를 시행하였다. 크기 1.5 cm 미만의 양성및 악성 갑상선 결절군과 크기 1.5 cm 이상의 양성 및 악성결절로 그룹을 나누고 각 군에서 나이, 성별, 갑상선 기능검사, 항갑상선 항체, 갑상선 초음파 및 미세침흡인세포검사등을 검토하였고, 모든 갑상선 결절에 Koike (6)가 제한한 초음파지표 점수(Ultrasonographie index point)를 부여하여 각 군을 비교하였다. 결과: 분석한 갑상선 결절 372예 중 악성결절의 유병율은 18.0% (67예)였다. 갑상선 우연 종의 유병율은 81.5% (303예)였다. 갑상선 우연 종에서의 악성률은 17.5% (53예)로 나왔다. 크기 1.5 cm 이상의 양성 및 악성 갑상선 결절과 양성 및 악성 갑상선 우연종에서 나이, 성별, 갑상선 기능검사, 항갑상선항체에는 의미있는 차이가 없었다. 또한 양성 및 악성우연종에서 의 갑상선 결절크기에도 의미있는 차이는 보이지 않았다. 갑상선 결절의 초음파 지표점수만이 양성 및 악성우연종과 양성 및 악성갑상선 결절의 감별에 의미있는 차이를 보였다. 갑상 선우연종과 크기 1.5 cm 이상의 갑상선 결절에 서 양성을 나타내는 초음파지표점수는 각각 3 점과 4점으로 다르게 나타났다. 양성 및 악성 갑상선우연종의 감별에서 초음파 지표점수의 민감도는 93.6%, 특이도는 52.8%, 양성예측율은 92.4%로 나왔고, 진단적 효율은 86.4% 였으며 크기 1.5 cm 이상의 양성 및 악성 갑상선 결정의 감별에서 초음파지수 민감도는 92.7%, 특이도가 42.9%, 양성 예측도 86%, 효율 82.6%를 보였다. 결론: 갑상선결절에서의 양성 및 악성의 유무는 임상적으로 판단하기 힘들지만 갑상선 결절에서의 초음파 소견 및 초음파 지표 점수를 도입하면 이에 대한 감별에 도움을 줄 수 있다. 따라서 갑상선 초음파검사시 초음파지표점수의 사용은 향후 갑상선 결절의 진단 방향을 제시하는 중요한 길잡이가 될 수 있으리라 사료된다.