• Molecules and Cells
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• 제42권7호
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• pp.503-511
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• 2019

As sessile organisms, plants have developed sophisticated system to defend themselves against microbial attack. Since plants do not have specialized immune cells, all plant cells appear to have the innate ability to recognize pathogens and turn on an appropriate defense response. The plant innate immune system has two major branches: PAMPs (pathogen associated molecular patterns)-triggered immunity (PTI) and effector-triggered immunity (ETI). The ability to discriminate between self and non-self is a fundamental feature of living organisms, and it is a prerequisite for the activation of plant defenses specific to microbial infection. Arabidopsis cells express receptors that detect extracellular molecules or structures of the microbes, which are called collectively PAMPs and activate PTI. However, nucleotidebinding site leucine-rich repeats (NB-LRR) proteins mediated ETI is induced by direct or indirect recognition of effector molecules encoded by avr genes. In Arabidopsis, plasmamembrane localized multifunctional protein RIN4 (RPM1-interacting protein 4) plays important role in both PTI and ETI. Previous studies have suggested that RIN4 functions as a negative regulator of PTI. In addition, many different bacterial effector proteins modify RIN4 to destabilize plant immunity and several NB-LRR proteins, including RPM1 (resistance to Pseudomonas syringae pv. maculicola 1), RPS2 (resistance to P. syringae 2) guard RIN4. This review summarizes the current studies that have described signaling mechanism of RIN4 function, modification of RIN4 by bacterial effectors and different interacting partner of RIN4 in defense related pathway. In addition, the emerging role of the RIN4 in plant physiology and intercellular signaling as it presents in exosomes will be discussed.

• Animal Bioscience
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• 제35권5호
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• pp.721-729
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• 2022

Objective: An experiment was conducted to determine the effects of supplementing graded concentrations of inorganic sulphur (S) without and with folic acid (FA) in maize-soybean meal diets on performance, slaughter and anti-oxidant variables, immune responses and serum protein fractions in broiler chicken. Methods: Inorganic S was supplemented at 0.05%, 0.10%, 0.15%, and 0.20% alone or in combination with FA (4 mg/kg) in basal diet (BD) containing no supplemental methionine (Met) and FA. A control group was fed with the recommended concentration of Met. Each diet was offered to 10 pens of 5 male broiler chicks (Cobb 400) and fed ad libitum from day 1 to 42. Results: The broilers fed the BD had lower body weight gain (BWG), feed efficiency (FE), higher lipid peroxidation (LP), lower activity of glutathione peroxidase (GSHPx), lower lymphocyte proliferation ratio (LPR), and reduced concentrations of total protein, albumin, and globulin in serum. Supplementation of FA and S to the BD improved the BWG (all concentrations of S) and FE (0.20% S) similar to the control group. Similarly, the combination of S and FA significantly improved the concentrations of total protein, albumin, and globulin in serum, reduced the LP and increased the activity of GSHPx and LPR. However, responses in the above parameters were related to the concentration of S in the diet. The slaughter variables and antibody titres against the Newcastle disease were not affected with the treatments. Conclusion: Based on the results, it is concluded that the combination of S (0.2%) and FA (4 mg/kg) improved the BWG and FE, similarly supplementation of these nutrients improved the concentration of protein fractions and reduced the stress (reduced LP and improved GSHPx) variables in serum and improved the cell mediated immune response (LPR) in broilers fed sub-optimal concentrations of Met in diet.

• Journal of Veterinary Science
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• 제24권5호
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• pp.72.1-72.16
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• 2023

Background: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) on the surface of Streptococcus dysgalactiae, coded with gapC, is a glycolytic enzyme that was reported to be a moonlighting protein and virulence factor. Objective: This study assessed GAPDH as a potential immunization candidate protein to prevent streptococcus infections. Methods: Mice were vaccinated subcutaneously with recombinant GAPDH and challenged with S. dysgalactiae in vivo. They were then evaluated using histological methods. rGAPDH of mouse bone marrow-derived dendritic cells (BMDCs) was evaluated using immunoblotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay methods. Results: Vaccination with rGAPDH improved the survival rates and decreased the bacterial burdens in the mammary glands compared to the control group. The mechanism by which rGAPDH vaccination protects against S. dysgalactiae was investigated. In vitro experiments showed that rGAPDH boosted the generation of interleukin-10 and tumor necrosis factor-α. Treatment of BMDCs with TAK-242, a toll-like receptor 4 inhibitor, or C29, a toll-like receptor 2 inhibitor, reduced cytokines substantially, suggesting that rGAPDH may be a potential ligand for both TLR2 and TLR4. Subsequent investigations showed that rGAPDH may activate the phosphorylation of MAPKs and nuclear factor-κB. Conclusions: GAPDH is a promising immunization candidate protein for targeting virulence and enhancing immune-mediated protection. Further investigations are warranted to understand the mechanisms underlying the activation of BMDCs by rGAPDH in a TLR2- and TLR4-dependent manner and the regulation of inflammatory cytokines contributing to mastitis pathogenesis.

• 한국식품영양과학회지
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• 제35권6호
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• pp.683-689
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• 2006

본 연구는 게르마늄강화효모 (germanium: 3,210 ppm, 400 mg${\times}$3회/day)가 인체의 혈청지질 및 면역세포 변화에 미치는 효과를 평가를 목적으로 $50{\sim}75$세의 남녀 50명을 대상으로 임상실험을 실시하였으며, 게르마늄강화효모 복용 전후에 따른 혈청지질 수준의 변화 및 면역증진 기능평가에 중요한 역할을 하는 NK세포, B세포, T세포 및 항암기능 효과를 지니는 $TNF-{\alpha}$의 생성의 변화를 확인하였다. 대조군과 보충군 모두 보충 전, 4주, 8주 후의 헤모글로빈, 헤마토크릿, 적혈구 지표(red blood cell indices) 및 백혈구 수, 혈소판, 혈당, ALT, AST, ALP, BUN, Cr, TB, TP, Alb, A/G ratio, ${\gamma}-globulin(g/dL)$이 보충에 따른 유의적인 차이는 나타나지 않았다. 총 콜레스테롤, LDL 콜레스테롤 및 HDL 콜레스테롤은 보충 전, 후에 따른 유의적인 차이는 나타나지 않았다. 중성지방의 경우 대조군에서는 보충 전, 후에 따른 유의적인 차이는 나타나지 않았으나, 게르마늄강화효모 보충군에서는 보충 전에 비해 보충 8주 후에는 p<0.05 수준에서 유의적으로 감소하는 것으로 나타났다. B세포의 경우 대조군에서는 보충 전, 후에 따른 유의적인 차이는 나타나지 않았으나, 게르마늄강화효모 보충군에서는 보충 전에 비해 보충 8주 후에는 p<0.05 수준에서 유의적으로 증가하는 것으로 나타났다. $TNF-{\alpha}$의 경우 대조군에서는 보충 전, 후에 따른 유의적인 차이는 나타나지 않았으나, 게르마늄강화효모 보충군에서는 보충 전에 비해 보충 8주 후에는 p<0.05 수준에서 유의적으로 증가하는 것으로 나타났다. 이는 게르마늄강화효모가 인체의 면역증진에 각종 암, 성인병의 예방과 치료, 인체 면역력의 증진 등 건강증진을 위한 새로운 기능성 원료로의 활용이 기대되며, 이에 대한 지속적인 연구가 사료 된다.

• Toxicological Research
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• 제34권1호
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• pp.7-12
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• 2018

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T ($T_H1$) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of $T_H1$ cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

• 미생물학회지
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• 제50권4호
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• pp.281-284
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• 2014

병원성 균주인 녹농균(Pseudomonas aeruginosa) 감염에 대응하여 나타나는 면역반응은 인체의 항상성 유지에 중요하다. 선행 연구에서 녹농균의 감염에 대응하여 bradykinin receptor (BR)의 발현이 증가됨을 보고하였지만, 발현유도에 관여하는 녹농균 유래인자에 대해서는 보고한 바가 없었다. 이번 연구에서는 녹농균에 의한 BR의 발현은 Type III secretion system (T3SS)이 관여하지만, 기존에 알려진 T3SS인자가 아닌 nucleoside diphosphate kinase (Ndk)에 의한 것으로 조사되었다. 하지만 pDNNDK를 이용한 transfection 실험 결과, Ndk 만으로는 BR의 발현이 유도되지 않았으며, Ndk와 함께 flagella가 필요함을 발견하였다. 이러한 결과는 기존에 보고된 주요 pathogen-associated molecular patterns (PAMPs)인 flagella와 더불어 감염대응에 관여하는 Ndk를 발굴한 의미가 있으며, 녹농균에 의한 질병기전을 이해하는데 도움을 줄 수 있다.

• Parasites, Hosts and Diseases
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• 제62권1호
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• pp.30-41
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• 2024

The dense granule protein of Toxoplasma gondii, inhibitor of signal transducer and activator of transcription 1 (IST) is an inhibitor of signal transducer and activator of transcription 1 (STAT1) transcriptional activity that binds to STAT1 and regulates the expression of inflammatory molecules in host cells. A sterile inflammatory liver injury in pathological acute liver failures occurs when excessive innate immune function, such as the massive release of IFN-γ and TNF-α, is activated without infection. In relation to inflammatory liver injury, we hypothesized that Toxoplasma gondii inhibitor of STAT1 transcription (TgIST) can inhibit the inflammatory response induced by activating the STAT1/IRF-1 mechanism in liver inflammation. This study used IFN-γ and TNF-α as inflammatory inducers at the cellular level of murine hepatocytes (Hepa-1c1c7) to determine whether TgIST inhibits the STAT1/IRF-1 axis. In stable cells transfected with TgIST, STAT1 expression decreased with a decrease in interferon regulatory factor (IRF)-1 levels. Furthermore, STAT1 inhibition of TgIST resulted in lower levels of NF-κB and COX2, as well as significantly lower levels of class II transactivator (CIITA), iNOS, and chemokines (CLXCL9/10/11). TgIST also significantly reduced the expression of hepatocyte proapoptotic markers (Caspase3/8/9, P53, and BAX), which are linked to sterile inflammatory liver injury. TgIST also reduced the expression of adhesion (ICAM-1 and VCAM-1) and infiltration markers of programmed death-ligand 1 (PD-L1) induced by hepatocyte and tissue damage. TgIST restored the cell apoptosis induced by IFN-γ/TNF-α stimulation. These results suggest that TgIST can inhibit STAT1-mediated inflammatory and apoptotic responses in hepatocytes stimulated with proinflammatory cytokines.

• 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.

• 동의생리병리학회지
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• 제16권5호
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• pp.921-927
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• 2002

Inflammation is localized response to foreign substance such as bacteria or in some instance to internally produced substances and has relation with immunity system. The macrophages plays a role in the development of the Iymphohaemopoietic system before and after birth, as well as in the natural and acquired immune responses of adult to immunogens, including infectious agents. NO have been suggested to play an important role in endotoxin-mediated shock and imflammation. In this study, we investigated the effect of Omisodok-eum on the production of NO. The Omisodok-eum inhibited the secretion of NO in LPS-stimulated mouse peritoneal macrophages, without affecting cell viability. The protein level of inducible nitric oxide synlhase(iNOS) in peritoneal macrophages was also decreased by Omisodok-eum. These results suggest that Omisodok-eum suppresses the endotoxin-induced inflammatory responses through inhibiting the production of NO

• 생물정신의학
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• 제19권4호
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• pp.164-171
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• 2012

The placebo effect, a response observed during the placebo arm of a clinical trial, is produced by the psychobiological action of the placebo as well as by other potential contributors to symptom amelioration such as spontaneous improvement, regression to the mean, biases, concurrent treatments, and study design. From a psychological viewpoint, there are many mechanisms that contribute to placebo effects, including expectations, conditioning, learning, and anxiety reduction. Placebo responses are also mediated by opioid and non-opioid mechanisms including dopamine, serotonin, cholecystokinin, and immune mediators. During recent years, a trend towards increased placebo effects in clinical trials of neuropsychiatric drugs has been noted. Indeed, the placebo effects observed in clinical trials constitute an increasing problem and interfere with signal-detection analyses of potential treatments. Several potential factors including protocol/study design and conduct related factors may account for the placebo effect observed in clinical trials. This paper reviews key issues related to this problem and aims to identify potential solutions.