• 한국동물위생학회지
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• 제42권4호
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• pp.201-216
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• 2019

Porcine reproductive and respiratory syndrome (PRRS) is characterized by reproductive failure in sows and respiratory distress in all age pigs. Porcine respiratory disease complex (PRDC) is a disease caused by opportunistic bacterial infection secondary to a weakened immune system by a preceding respiratory infection. In this study, we tried to compare the immune responses in PRRS and PRDC groups to clearly characterize the disease severity. Eighty-five pigs were infected with various Korean field PRRS virus strains. Infected animals were classified into PRRS (n=32) and PRDC (n=53) groups based on lung lesions such as interstitial pneumonia, suppurative pneumonia, and pleuropneumonia. The immune cell population of bronchoalveolar lavage cells (BALc) was evaluated on 14 and 28 days post infection (dpi) and PMBC cytokine expression was measured on 0, 3, 7, 14 dpi to investigate early inflammatory reactions. Pulmonary lesion severity was negatively correlated with alveolar macrophage (AM) in both PRRS and PRDC groups on 14 and 28 dpi. AM in BALc was less populated in PRDC group on 28 dpi compared to PRRS group. AM in BALc was significantly less populated in PRDC group on 28 dpi compared to 14 dpi. In addition, cytotoxic T lymphocyte (CTL) in BALc was higher populated in PRDC group on 14 dpi and 28 dpi compared to PRRS group. In the case of PBMC cytokine TNF-α, IFN-α, IL-1β, IFN-γ, FoxP3, and IL-2, the PRRS group showed higher expression than the PRDC group on 7 dpi, 14 dpi, 7 dpi, 14 dpi, 14 dpi, and 14 dpi, respectively. On the other hand, in the case of IFN-β, IL-6, IL-8, IL-4, and IL-17, the PRDC group showed higher PBMC cytokine expression at 14 dpi, 7 dpi, 14 dpi, 3 dpi, and 3 dpi, respectively, than the PRRS group. Based on these results, our study could characterize differential immune responses in pigs with PRRS or PRDC.

• IMMUNE NETWORK
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• 제11권1호
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• pp.79-94
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• 2011

Background: Dendritic cell (DC)-based vaccines are currently being evaluated as a novel strategy for tumor vaccination and immunotherapy. However, inducing long-term regression in established tumor-implanted mice is difficult. Here, we show that deoxypohophyllotoxin (DPT) induces maturation and activation of bone marrow-derived DCs via Toll-like receptor (TLR) 4 activation of MAPK and NF-${\kappa}B$. Methods: The phenotypic and functional maturation of DPT-treated DCs was assessed by flow cytometric analysis and cytokine production, respectively. DPT-treated DCs was also used for mixed leukocyte reaction to evaluate T cell-priming capacity and for tumor regression against melanoma. Results: DPT promoted the activation of $CD8^+$ T cells and the Th1 immune response by inducing IL-12 production in DCs. In a B16F10 melanoma-implanted mouse model, we demonstrated that DPT-treated DCs (DPT-DCs) enhance immune priming and regression of an established tumor in vivo. Furthermore, migration of DPT-DCs to the draining lymph nodes was induced via CCR7 upregulation. Mice that received DPT-DCs displayed enhanced antitumor therapeutic efficacy, which was associated with increased IFN-${\gamma}$ production and induction of cytotoxic T lymphocyte activity. Conclusion: These findings strongly suggest that the adjuvant effect of DPT in DC vaccination is associated with the polarization of T effector cells toward a Th1 phenotype and provides a potential therapeutic antitumor immunity.

• IMMUNE NETWORK
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• 제7권3호
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• pp.109-116
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• 2007

Background: Human papillomavirus (HPV) infection is responsible for cervical cancer, a common cancer in women. Since HPV infection and cancer development are controlled by the host immune system, immunotherapy against HPV can be helpful in preventing or treating HPV-associated cervical cancer. Two oncoproteins of HPV16, E6 and E7, are promising targets for immunotherapy against cervical cancer, because they are constitutively expressed in cervical cancer. Methods: Since cellular vaccines using B cells as well as dendritic cells offer an efficient approach to cancer immunotherapy, we opted to use B cells. We evaluated the immunogenicity and anti-tumor effects of a B cell vaccine transduced with HPV16 E6/E7-expressing adenovirus. Results: Vaccination with HPV16 E6/E7-transduced B cells induced E6/E7-specific $CD8^+$ T cell-dependent immune responses and generated anti-tumor effects against E6/E7-expressing TC-1 tumor. The anti-tumor effect induced by this B cell vaccine was similar to that elicited by DC vaccine, showing that B cells can be used as an alternative to dendritic cells for cellular vaccines. Conclusion: Thisstudy has shown the feasibility of using B cells as immunogenic APCs and the potential for developing prophylactic and therapeutic vaccines against HPV-associated cervical cancer using a B cell vaccine transduced with adenovirus expressing HPV16 E6/E7.

• 대한두경부종양학회지
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• 제19권1호
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• pp.25-33
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• 2003

Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.

• 대한본초학회지
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• 제37권3호
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• pp.29-39
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• 2022

Objective : This study is aimed to evaluate the protective effects of Rehmanniae Radix, Mori Folium, and Liriopie Tuber mixture (RML) on lung injury of Particulate matter less than 10 um in diameter and diesel exhaust particles (PM10D) mice model. Methods : To investigate the anti-inflammatory activity of RML, PM10D was diluted in aluminum hydroxide (Alum) in 7-week-old male mice and induced by Intra-Nazal-Tracheal (INT) injection method. Animal experiments were divided into 5 groups. Nor (normal mice), CTL (PM10D-induced mice with the administration of distilled water), DEXA (PM10D-induced mice with the administration of 3 mg/kg Dexamethasone), RML 100 (PM10D-induced mice treated with RML 100 mg/kg weight), and RML 200 (PM10D-induced mice treated with RML 200 mg/kg body weight). After 11 days administration, mice were sacrificed and inflammation-related immune cells in broncho-alveolar lavage fluid (BALF) were analyzed. Inflammation-related biomarkers were also analyzed in blood and lungs. Lung tissue was observed through histological examination. Results : In the PM10D induced model, the PML showed decreases in CXCL-1 and IL-17A in BALF. Expression of inflammatory cytokines and cough-related mRNA genes was significantly decreased in serum and lung tissue. The mixture treatment of RML significantly improved the immune related cells in the serum. In addition, histological observations showed a tendency to decrease the severity of lung injury. Conclusions : Overall, these results confirmed the respiratory protective effect of the RML mixture in a model of lung injury induced by air pollution (PM10+DEP), suggesting that it is a potential treatment for respiratory damage.

• IMMUNE NETWORK
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• 제22권5호
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• pp.42.1-42.20
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• 2022

Vaccination with tumor peptide epitopes associated with MHC class I molecules is an attractive approach directed at inducing tumor-specific CTLs. However, challenges remain in improving the therapeutic efficacy of peptide epitope vaccines, including the low immunogenicity of peptide epitopes and insufficient stimulation of innate immune components in vivo. To overcome this, we aimed to develop and test an innovative strategy that elicits potent CTL responses against tumor epitopes. The essential feature of this strategy is vaccination using tumor epitope-loaded nanoparticles (NPs) in combination with polyinosinic-polycytidylic acid (poly-IC) and anti-PD1 mAb. Carboxylated NPs were prepared using poly(lactic-co-glycolic acid) and poly(ethylene/maleic anhydride), covalently conjugated with anti-H-2K^b mAbs, and then attached to H-2K^b molecules isolated from the tumor mass (H-2^b). Native peptides associated with the H-2K^b molecules of H-2K^b-attached NPs were exchanged with tumor peptide epitopes. Tumor peptide epitope-loaded NPs efficiently induced tumor-specific CTLs when used to immunize tumor-bearing mice as well as normal mice. This activity of the NPs significantly was increased when co-administered with poly-IC. Accordingly, the NPs exerted significant anti-tumor effects in mice implanted with EG7-OVA thymoma or B16-F10 melanoma, and the anti-tumor activity of the NPs was significantly increased when applied in combination with poly-IC. The most potent anti-tumor activity was observed when the NPs were co-administered with both poly-IC and anti-PD1 mAb. Immunization with tumor epitope-loaded NPs in combination with poly-IC and anti-PD1 mAb in tumor-bearing mice can be a powerful means to induce tumor-specific CTLs with therapeutic anti-tumor activity.

• IMMUNE NETWORK
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• 제21권5호
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• pp.33.1-33.19
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• 2021

IL-1β plays critical roles in the priming and effector phases of immune responses such as the differentiation, commitment, and memory formation of T cells. In this context, several reports have suggested that the IL-1β signal is crucial for CTL-mediated immune responses to viral infections and tumors. However, little is known regarding whether IL-1β acts directly on CD8⁺ T cells and what the molecular mechanisms underlying expression of IL-1 receptors (IL-1Rs) on CD8⁺ T cells and features of IL-1R⁺ CD8⁺ T cells are. Here, we provide evidence that the expression of IL-1R type I (IL-1RI), the functional receptor of IL-1β, is preferentially induced by IL-21 on TCR-stimulated CD8⁺ T cells. Further, IL-1β enhances the effector function of CD8⁺ T cells expressing IL-21-induced IL-1RI by increasing cytokine production and release of cytotoxic granules containing granzyme B. The IL-21-IL-1RI-IL-1β axis is involved in an augmented effector function through regulation of transcription factors BATF, Blimp-1, and IRF4. Moreover, this axis confers a unique effector function to CD8⁺ T cells compared to conventional type 1 cytotoxic T cells differentiated with IL-12. Chemical inhibitor and immunoprecipitation assay demonstrated that IL-21 induces a unique pattern of STAT activation with the formation of both STAT1:STAT3 and STAT3:STAT5 heterodimers, which are critical for the induction of IL-1RI on TCR-stimulated CD8⁺ T cells. Taken together, we propose that induction of a novel subset of IL-1RI-expressing CD8⁺ T cells by IL-21 may be beneficial to the protective immune response against viral infections and is therefore important to consider for vaccine design.

• 한국콘텐츠학회논문지
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• 제17권6호
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• pp.81-85
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• 2017

본 연구는 컴퓨터단층촬영을 이용한 요로결석 검사에서 저선량 CT(Low dose Computed Tomography) 프로토콜의 적용에 따른 유용성을 평가하였다. 연구대상은 2016년 6월-12월까지 부산지역 일개 의료기관을 내원한 비뇨기계 환자이며 연구에 이용된 프로토콜은 통계적 반복 재구성법(Adaptive Statistical Iterative Reconstruction, ASIR)을 50% 적용한 저선량 CT 프로토콜이다. 정량적 분석 결과 횡단면상(Axial image)의 신장의 관심 영역(region of image. ROI) 내 평균 화소 값과 표준편차는 복부촬영 프로토콜 $26.21{\pm}7.08$, 저선량 CT 프로토콜 $20.03{\pm}8.16$이며 관상면(Coronal imalge) 영상에서 신장의 관심영역 내 평균 화소 값과 표준편차는 복부촬영 프로토콜 $22.07{\pm}7.35$, 저선량 CT 프로토콜 $21.67{\pm}6.11$이었다. 정성적 분석결과 인공물에 대한 4명의 관찰자 평균값은 복부촬영 프로토콜 $19.14{\pm}0.36$, 저선량 CT 프로토콜 $19.17{\pm}0.43$이며 해상도 및 대조도의 평균값은 복부촬영 프로토콜 $19.35{\pm}0.70$, 저선량 CT 프로토콜 $19.29{\pm}0.58$이었다. 피폭선량 분석 결과 복부촬영 프로토콜의 CTDIvol 평균값은 18.02 mGy, DLP 평균값은 $887.51mGy{\cdot}cm$이며 저선량 CT 프로토콜 CTDIvol 평균값은 7.412 mGy, DLP 평균값은 $361.22mGy{\cdot}cm$이었다. 이로 인한 선량의 감소율은 각 58.82%, 59.29% 이었다.

• 한국축산식품학회지
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• 제32권2호
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• pp.190-197
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• 2012

본 연구는 국화과 구근 작물인 야콘을 이용하여 농도별(0.05, 0.1, 0.25, 0.5, 1%)로 야콘 에탄올 추출물(YEE)과 야콘 착즙액(YPE)의 항산화 활성을 평가했다. 그 결과 철이온 흡착력과 linoleic acid 과산화 억제능 및 추출 수율에서 야콘 착즙액이 야콘 에탄올 추출물보다 더 높은 활성을 나타내었다(p<0.05). 특히 철이온 흡착력에서 YPE가 0.5% 수준에서 약 80% 정도의 활성을 보였고, linoleic acid 과산화 억제능에서는 70% 이상의 매우 높은 활성을 띄었다. DPPH 라디칼 소거능과 환원력에서는 두 추출물 모두 0.5% 수준 이상에서 높은 활성을 보였다(p>0.05). 이러한 결과를 토대로 0.5%의 YEE와 YPE를 각각 돈육패티에 적용하였고, 대조구로는 BHT 0.01%를 이용하여 냉장저장 기간 동안(0, 3, 7, 10, 14일) 이화학적 특성 및 미생물 검사를 실시하였다. 그 결과 pH와 백색도, 황색도에서 각 처리구에 따른 유의적인 차이를 보이지 않았으나(p>0.05) 저장기간이 경과함에 따라 증가하는 경향을 보였고, 반면 적색도에서는 처리구별로 대조구가 가장 높고 REF(BHT 0.01%), TRT1(YEE), TRT2(YPE) 순서로 낮아지는 경향을 보였으나 10일이후부터는 대조구와 유의차가 없었고(p>0.05), 저장기간이 경과할수록 유의적으로 낮아졌다(p<0.05). 미생물 결과는 처리구별 차이는 없었으나(p>0.05), 7일 경과 후부터 모든 처리구가 급격히 증가하였다(p<0.05). TBARS값도 저장기간이 경과함에 따라 증가하는 경향을 보였으며(p<0.05), 야콘 착즙액 처리구와 에탄올 추출물 처리구간에 차이는 없었으나(p>0.05), 착즙액의 경우 대조구에 비하여 낮음으로써 항산화 활성을 보였다(p>0.05). 이와 같은 연구결과로 볼 때 야콘 착즙액이 지방 산화억제를 위한 천연의 항산화제로 식육가공품에 사용 가능성이 있을 것으로 판단된다.

• 한국축산식품학회지
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• 제32권4호
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• pp.497-503
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• 2012

본 연구는 인공합성 항산화제를 대신할 천연 추출물을 사용한 항산화제 개발을 목적으로 레드비트를 이용하였다. 먼저 항산화 활성을 알아보기 위하여 레드비트 에탄올 추출물(RBW)과 레드비트 물 추출물(RBW)을 각각(0.05-1.0%) 농도로 희석하여 항산화 활성을 평가하였다. 그 결과 DPPH 라디칼 소거능과 철이온 흡착력에서 레드비트물 추출물(RBW)이 레드비트 에탄올 추출물(RBE) 보다 유의적 차이를 보이며 더 높은 활성을 보였다(p<0.05). 특히 철이온 흡착력에서 RBW는 0.1% 농도부터 87.0%의 높은 활성을 보였고, 1.0% 첨가에서는 100%의 활성을 보였다. 또한 DPPH 라디칼 소거능에서도 0.25%부터 60% 정도의 높은 활성을 보였다. 반면, 환원력에서는 RBE가 유의적으로 더 높은 활성을 보였다(p<0.05). Linoleic acid 과산화 억제능에서는 두 처리구간 유의적인 차이를 보이지 않았지만(p>0.05), RBW는 모든 농도에서 83% 이상의 활성을 보였고, RBE는 0.05%에서 80% 정도의 활성을 보였다. 이를 토대로 0.5%의 RBE와 RBW를 각각 돈육패티에 적용하였고, 참조구로는 BHT 0.01%를 이용하여 저장기간 동안(0-14일) 이화학적 특성 및 미생물 검사를 실시하였다. 그 결과 백색도와 황색도는 처리구별, 그리고 저장기간에 따른 유의적인 차이를 보이지 않았으며(p<0.05), pH와 적색도는 저장기간이 길어짐에 따라 유의적으로 더 높아졌다(p>0.05). 미생물에서는 총균과 대장균군 모두 참조구가 다른 처리구와 유의적으로 낮은 값을 보였고(p>0.05), 저장기간이 경과함에 따라 유의적인 차이를 보이며 증가하였다(p>0.05). 그리고 지방산화 억제 활성을 평가한 TBARS에서는 냉장 저장 중 대조구(CTL)가 유의적으로 가장 높은 값을 보였고, 레드비트 처리구와 유의적인 차이를 보였다(p<0.05). 특별히 레드비틀 첨가한 TRT1과 TRT2는 저장기간 동안 REF와 유의적인 차이를 보이지 않아(p<0.05) 우수한 지방산화 억제능력을 보였다.