• International Journal of Oral Biology
• /
• 제34권1호
• /
• pp.29-36
• /
• 2009

Cyclosporin A (CsA) has been used clinically as an immunosuppressive drug to prevent organ transplant rejection and in basic research as a mitochondrial permeability blocker. It has been reported that CsA has a protective role in severed neurons and a neurotrophic effect in neuronal cells. However, the molecular mechanisms underlying the stimulation of neuronal cell proliferation by CsA have not yet been elucidated. In our current study, we investigated CsA responsive proteins in PC12 cells using a systematic proteomic approach. The viability of these cells following CsA treatment increased in a dose- and time-dependent manner. Proteins in the CsA-treated PC12 cells were profiled by two-dimensional gel electrophoresis (2-DE) and identified by matrix-assisted laser desorption ionization time-of flight (MALDI-TOF) and electrospray ionization quadupole time-of-flight mass spectrometries (EIQ-TOFMS). This differential expression analysis showed significant changes for 10 proteins (6 up-regulated and 4 down-regulated) upon CsA treatment that were related to cell proliferation, metabolism and the stress response. These proteomics data further our understanding of the proliferation mechanisms of PC12 cells exposed to CsA and demonstrate that our methodology has potential to further elucidate the mechanisms and pathways involved.

• Journal of Periodontal and Implant Science
• /
• 제30권4호
• /
• pp.747-757
• /
• 2000

Cyclosporin A(CsA) is an immunosuppressive agent widely used for preventing graft rejecting response in organ transplantation. The basic properties of CsA to osteoblast has not been well known yet. A better understanding of the mechanisms of CsA function on bone could provide valuable information regarding basic properties of bone remodeling, pharmacotherapeutic intervention in metabolic bone disease, and the consequences of immunosuppression in bone physiology. The purpose of this study was to investigate the effect of CsA on osteoblast by evaluating parameters of proliferation, collagen synthetic activity, alkaline phosphatase activity, and ALP mRNA expression in mouse calvarial cell. 1. CsA ($3{\mu}g/m{\ell}$) treated mouse calvarial cell showed statistically significant increase in cell proliferation.(P<0.05) 2. CsA($1,\; 3{\mu}g/m{\ell}$) treated MC3T3 cell line showed statistically significant increase in cell proliferation. 3. The amount of collagen of CsA($3{\mu}g/m{\ell}$) treated mouse calvarial cell was decreased statistically significantly. 4. Alkaline phosphatase activity was increased statistically significantly in CsA treated group($1{\mu}g/m{\ell}$). 5. mRNA expression of ALP was increased in CsA treated group These results suggest that CsA could affect bone remodeling by modulating proliferation & differentiation of osteoblast.

• Journal of Ginseng Research
• /
• 제12권1호
• /
• pp.63-67
• /
• 1988

인삼사포닌 분획물들(total saponin, diol saponin and triol saponin)이 생쥐의 항체생성에 미치는 영향과 면역억제의 회복에 미치는 영향 그리고 혈청총단백질의 생성에 미치는 영향에 대하여 알아본 결과 아래와 같은 결론을 얻었다. 1. Total saponin은 10mg/kg/day, diol saponin은 10mg/kg/day, triol saponin은 5mg/kg/day로 생쥐에 투여하였을 때 순환성 항체가 가장 많이 생성되는 것으로 나타났다. 2. CY로 면역을 억제시킨 상태에서는 인삼사포닌을 투여하여도 순환성 항체의 생성이 대조군과 차이가 없는 것으로 나타났다. 3. 인삼사포닌은 항체생성과 혈청총단백질의 증가에 서로 다른 농도로 작용을 나타낸다.

• 약학회지
• /
• 제58권2호
• /
• pp.81-90
• /
• 2014

In order to determine the functional benefits of Cordyceps militaris in the immune system, we examined the immunomodulatory activities of C. militaris using an immunocompromised C57BL/6 mice, mouse spleen cells, RAW 264.7 macrophage cells, and A549 lung carcinoma cells. Mice were injected intraperitioneally with an immunosuppressive drug, cyclophosphamide, and then administered orally with 30, 100 and 300 mg/kg of 50% ethanol extract of C. militaris (CME 30, CME 100 and CME 300) for 14 days. CME increased splenocyte proliferation and natural killer (NK) cell activity compared to 3% hydroxypropyl methylcellulose-treated control mice. CME also increased the production of Th1 cytokines, IL-2 and TNF-${\alpha}$ in spleen cells isolated from CME-injected mice and in vitro, which suggested the enhanced cellular immunity in response to CME. CME also increased splenocyte proliferation, NK cell activity, and IL-2 and TNF-${\alpha}$ production compared to 1 ${\mu}M$ methotrexate-treated spleen cells in vitro. We examined whether C. militaris regulates the production of inflammatory mediators in LPS-stimulated RAW 264.7 cells. CME inhibited LPS-induced NO production and iNOS expression in a dose dependent manner, while COX-2 expression was remained unchanged. In addition, CME also has free radical scavenging activity, indicating its antioxidant activity. These results indicate that C. militaris enhances immune activity by promoting immune cell proliferation and cytokine production.

• International Journal of Industrial Entomology and Biomaterials
• /
• 제23권2호
• /
• pp.223-229
• /
• 2011

Cyclophilins are originally identified as cytosolic binding protein of the immunosuppressive drug cyclosporine A. They have an activity of peptidyl prolyl cis/trans-isomerases (PPIase), which may play important roles in protein folding, trafficking, assembly and cell signaling. In this study, we report the cloning and characterization of a Bombyx mori cyclophilin A (bCypA) cDNA. The full-length cDNA of bCypA consist of 947 nucleotides with a polyadenylation signal sequence AATAAA and contain an open reading frame of 498 nucleotides encoding a polypeptide of 166 amino acids. The deduced amino acid sequence of bCypA shares a central peptidyl prolyl cis/trans-isomerase and a cyclosporin-A-binding domain with other cyclophilin sequences. Relative quantification real-time (RT) PCR analysis shows that mRNA transcripts of bCypA are detected in all the investigated tissues and highest expression level in the skin of 3-day-old 5 instar larva. Also, bCypA had PPIase activity on the proline-containing peptides. Accordingly, we suggest that bCypA is a new member of the cyclophilin A (CyPA) family and will be useful for quality control of bioactivity recombinant proteins with proline-containing peptides.

• 한방안이비인후피부과학회지
• /
• 제33권3호
• /
• pp.115-124
• /
• 2020

Objectives : The purpose of this study is to investigate the effect and side effects of steroids on dermatitis and skin barrier through lipid metabolism. And to propose using Herbal medicine to suppress Steroid rebound and prevent side effects. Methods : We reviewed recent studies about the relationship between dermatitis, skin lipid, steroid, and herbal medicine through Google scholar. Results : In various inflammatory skin diseases, the corticosteroid is selected as the primary drug due to its strong anti-inflammatory and immunosuppressive effect. However, long-term use of steroids has a variety of side effects, especially lipid metabolism disruption, which aggravates skin barrier damage underlying various skin diseases and is more susceptible to inflammatory reactions. Conclusions : Herbal medicine is used as a comprehensive approach, and it can be used to reduce the frequency of steroid exposure by protecting against barrier damage by controlling anti-inflammatory, antioxidant, and systemic/sebaceous lipid metabolism and stratum corneum protein differentiation.

• KSBB Journal
• /
• 제26권5호
• /
• pp.386-392
• /
• 2011

Human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig), an immunosuppressive agent, was expressed in transgenic rice cells using RAmy3D promoter and RAmy1A signal peptide for the inducible production and secretion into culture media by sugar depletion. In this study, sodium butyrate was used as a small molecular enhancer (SME) to enhance the production of hCTLA4Ig in transgenic rice cell suspension cultures. When 1 mM sodium butyrate was added in sugar-free media, relative viability was not reduced, while the productivity was improved 1.3-fold. In addition, by supplementing 87 mM sodium pyruvate as an alternative energy source during the production phase, death rate of the cells was decreased. When sodium pyruvate was not added, most cells became dead at day 6. However, by adding sodium pyruvate, 18% of viability can be maintained until day 10 and the production of hCTLA4Ig was enhanced 1.4-fold. When the combination of sodium pyruvate and sodium butyrate at optimum concentrations was added, the highest viability and hCTLA4Ig production could be obtained. The highest level of hCTLA4Ig reached up to 35 mg/L at day 10.

• 한국임상수의학회지
• /
• 제24권2호
• /
• pp.244-246
• /
• 2007

20 개월령의 알라스칸 말라뮤트 견에서 특발성 다발성근염의 임상증상과 병리학적 소견을 서술하였다. 임상 증상은 급성 허약을 동반한 진행성 운동불내성, 근 위축, 후지의 동시적 걸음걸이, 계란 위를 발끝으로 걷듯 짧고 경직된 걸음 등을 보였다. 신체검사와 임상검사에서는 신경계나 골격계 그리고 다른 질병과 관련된 이차적인 근 질환의 증거가 없었다. 그래서 가장 근 위축이 심한 부위에서 병리조직 검사를 위한 근 생검을 실시하였다. 골격근의 병리검사 결과 근 섬유의 괴사와 함께 단핵세포의 침윤이 관찰되어, 특발성 다발성근염으로 진단하였다. 초기치료는 통증경감과 보조치료를 시작하여 프레드니손 2 mg/kg를 경구로 매일 투여하는 면역억제 요법을 시행하였다. 3주 후 환자는 혈액, 혈청학적 검사에서 정상으로 회복될 뿐만 아니라 걸음걸이, 식욕, 운동의 향상을 나타냈다.

• Biomolecules & Therapeutics
• /
• 제28권1호
• /
• pp.34-44
• /
• 2020

Mesenchymal stem cells (MSCs) have been proposed as an alternative therapy to be applied into several pathologies of the nervous system. These cells can be obtained from adipose tissue, umbilical cord blood and bone marrow, among other tissues, and have remarkable therapeutic properties. MSCs can be isolated with high yield, which adds to their ability to differentiate into non-mesodermal cell types including neuronal lineage both in vivo and in vitro. They are able to restore damaged neural tissue, thus being suitable for the treatment of neural injuries, and possess immunosuppressive activity, which may be useful for the treatment of neurological disorders of inflammatory etiology. Although the long-term safety of MSC-based therapies remains unclear, a large amount of both pre-clinical and clinical trials have shown functional improvements in animal models of nervous system diseases following transplantation of MSCs. In fact, there are several ongoing clinical trials evaluating the possible benefits this cell-based therapy could provide to patients with neurological damage, as well as their clinical limitations. In this review we focus on the potential of MSCs as a therapeutic tool to treat neurological disorders, summarizing the state of the art of this topic and the most recent clinical studies.

• 대한두경부종양학회지
• /
• 제24권1호
• /
• pp.64-68
• /
• 2008

Purpose：The chronic use of immunosuppressive therapy in transplant recipients can increase the long-term risk of carcinoma. The aim of this study was to determine the incidence, biological behaviors, and treatment outcomes in PTC(papillary thyroid carcinoma) in renal allograft recipients. Material and Methods：The present study examined the incidence and biological behavior of PTCs in RA recipients. A total of 1,739 RA patients treated between January 1986 and December 1999 were followed-up for a median 137(84-238) months. During the follow-up period, 129(7.4%) recipients were identified as having posttransplant malignancies. Of those, 12(0.7%) had PTCs, and these comprised six male and six female patients with a median age of 41(23-57) years. Results：Nine cases(incidentalomas) were diagnosed based on ultrasonography(US) screening. Eight of those nine were TNM stage I, and two of the three clinical carcinomas were TNM stage IVa. During a median follow-up of 94(18-159) months, two(16.7%) PTC patients developed loco-regional recurrence, but no patients showed distant metastasis. Posttransplant PTC showed no gender bias, and was often associated with aggressive lymphatic metastasis. However, most incidentalomas showed a favorable treatment outcome. Conclusion：In conclusion, routine surveillance of the thyroid gland using US screening is recommended to ensure early detection, treatment and favorable prognosis in RA patients with PTC.