• Molecular & Cellular Toxicology
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• 제1권4호
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• pp.230-236
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• 2005

Formaldehyde is a common environmental contaminant found in tobacco smoke, paint, garments, diesel and exhaust, and medical and industrial products. Formaldehyde has been considered to be potentially carcinogenic, making it a subject of major environmental concern. However, only a little information on the mechanism of immunological sensitization and asthma by this compound has been known. So, we performed with Jurkat cell line, a human T lymphocyte, to assess the induction of DNA damage and to identify the DEGs related to immune response or toxicity by formaldehyde. In this study, we investigated the induction of DNA single strand breaks by formaldehyde using single cell gel electrophoresis assay (comet assay). And we compared gene expression between control and formaldehyde treatment to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based $GeneFishing^{TM}$ method. The cytotoxicity ($IC_{30}$) of formaldehyde was determined above the 0.65 mM in Jurkat cell in 48 h treatment. Based on the $IC_{30}$ value from cytotoxicity test, we performed the comet assay in this concentration. From these results, 0.65 mM of formaldehyde was not revealed significant DNA damages in the absence of S-9 metabolic activation system. And the one differentially expressed gene (DEG) of formaldehyde was identified to zinc finger protein 292 using $GeneFishing^{TM}$ method. Through further investigation, we will identify more meaningful and useful DEGs on formaldehyde, and then can get the information on the associated mechanism and pathway with immune response or other toxicity by formaldehyde exposure.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.946-953
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• 2002

Bisphenol A [2, 2 bis (4-hydoxyphenyl) propane; BPA] is a widely used endocrine disruptors and has estrogenic: activities. Although interests on biological effect of BPA are rising, evidences of its effect on immune system are lacking. We investigated that the effect of BPA on immune parameters to postulate the mechanism, and BPA interruptions between neuroendocrine and immune system. BPA was administrated to mice by p.o. (as a drinking water) dose on 0.015, 1.5 and 30 mg/ml for 4 weeks. The BPA treatment did not result in any change in body weight, spleen weight and distribution of lymphocyte subpopulation collected from spleen. BPA induced prolactin production in spleen, and exposure of SPA increased the activity of splenocyte proliferation in response to Con A (p<0.001). The production of a strong Th-1 type cytokine ($IFN-{\gamma}$) was induced while Th-2 type (IL-4) was suppressed by SPA treatment. These were consistent with RT-PCR results of transcription factor GATA-3 and IRF-1. These findings suggested that stimulation of prolactin production by estrogenic effects of SPA would affect cytokine profiles, and lead to imbalanced cellular immune response. In addition, we could speculate that prolactin and cytokine is important mediator involved in network between neuroendocrine and immune system by BPA.

• 대한한의학회지
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• 제32권3호
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• pp.10-17
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• 2011

Objective: To evaluate the immune-stimulatory potential of extracts of Broussonetia kazinoki Siebold (BK) on specific cellular and humoral immune responses in ovalbumin (OVA)-immunized mice. Material and Methods: C57BL/6 mice were immunized intraperitoneally with OVA/alum ($100{\mu}g/200{\mu}g$) on days 1, 8, and 15. BK (100, 300 or 1000 mg/kg) was given to mice orally for 21 days (from day 1 to day 21). At day 22, OVA-, lipopolysaccharide (LPS)- and concanavalin A (Con A)-stimulated splenocyte proliferation and OVA-specific and total antibodies were measured in plasma. Further, the effects of BK on expression of cytokine mRNA in OVA-immunized mice splenocytes were evaluated by RT-PCR analysis. Results: BK significantly enhanced OVA-, LPS-, and Con A-induced splenocyte proliferation in OVA-immunized mice (p<0.01). BK also significantly enhanced total IgM and OVA-specific IgG1 levels in plasma compared with the OVA control group. Moreover, BK up-regulated significantly the expression of mRNA level of IL-2 and IFN-${\gamma}$ in splenocytes. Conclusions: BK has immune-stimulating activity in an OVA-immunized mouse model system, enhancing the Th1 immune response. BK showed no cytotoxicity in this system, suggesting that BK may be a safe and effective adjuvant in humans.

• Molecules and Cells
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• 제24권2호
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• pp.247-254
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• 2007

Improvement in the pharmacokinetic properties of short interfering RNAs (siRNAs) is a prerequisite for the therapeutic application of RNA interference technology. When injected into mice as unmodified siRNAs complexed to DOTAP/Chol-based cationic liposomes, all 12 tested siRNA duplexes caused a strong induction of cytokines including interferon ${\alpha}$, indicating that the immune activation by siRNA duplexes is independent of sequence context. When modified by various combinations of 2'-OMe, 2'-F, and phosphorothioate substitutions, introduction of as little as three 2'-OMe substitutions into the sense strand was sufficient to suppress immune activation by siRNA duplexes, whereas the same modifications were much less efficient at inhibiting the immune response of single stranded siRNAs. It is unlikely that Toll-like receptor 3 (TLR3) signaling is involved in immune stimulation by siRNA/liposome complexes since potent immune activation by ds siRNAs was induced in TLR3 knockout mice. Together, our results indicate that chemical modification of siRNA provides an effective means to avoid unwanted immune activation by therapeutic siRNAs. This improvement in the in vivo properties of siRNAs should greatly facilitate successful development of siRNA therapeutics.

• 대한미생물학회지
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• 제16권1호
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• pp.49-55
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• 1981

최근(最近) 히스타민이 면역반응(免疫反應)을 조절(調節)함이 구명(究明)되고 있으나 생체내(生體內) 실험(實驗) 특(特)히 마우스에서의 연구보고(硏究報告)를 희소(稀少)하다. 본(本) 실험(實驗)에서는 histamine-2-receptor antagonist($H_2$ 차단제(遮斷劑))인 cimetidine과 히스타민이 마우스의 면양적혈구(緬羊赤血球)(SRBC)에 대(對)한 면역반응(免疫反應)에 미치는 영향(影響)을 실험(實驗)하였다. 마우스를 매일(每日) 14일간(日間) 여러가지 농도(濃度)의 cimetidine 으로 전처리(前處理)하고 여러가지 농도(濃度)의 SRBC($10^6,\;10^7$ 및 $10^8$ 세포(細胞))로 면역(免疫)하고 4일(日) 후(後)에 마우스 족척(足蹠)에 SRBC로 야기주사(惹起注射)하여 Arthus반응(反應)과 지연성과민반응(遲延性過敏反應)(DTH)를 족척종창반응(足蹠腫脹反應)으로 측정(測定)하였으며, 체액성면역반응(體液性免疫反應)은 적혈구응집소가(赤血球凝集素價)를 측정(測定)하였다. 수(數) 종(種) 농도(濃度)($10^{-1}M,\;10^{-3}M$, 및 $10^{-5}M$)의 히스타민을 야기주사(惹起注射)와 동시(同時)에 주사(注射)하여 24시간(時間)-DTH를 측정(測定)하여 히스타민 효과(效果)를 평가(評價)하였다. Cimetidine은 DTH를 항진(亢進)시켰으며 그 항진(亢進)은 250 ${\mu}g$의 cimetidine을 투여(投與)하였을 때 현저(顯著)하였다. 그러나 Arthus 반응(反應)과 혈청항체가(血淸抗體價)는 cimetidine 전처리(前處理) 군(群)과 대조군간(對照群間)에 유의(有意)한 차이(差異)가 없었다. 히스타민은 SRBC에 대(對)한 DTH를 투여량-의존성(投與量-依存性) 유형(類型)으로 억제(抑側)하였으며 그 억제(抑制)는 저농도(低濃度)의 항원량(抗原量)($10^6$ 및 $10^7$ SRBC)일때 더 현저(顯著)하였다. 그러나 외인성(外因性) 히스타민은 $10^8$ SRBC로 면역(免疫)하였을 때늘 DTH를 감소(滅少)시키지 않았다. 이상(以上)의 본(本) 실험결과(實驗結果)는 cimetidine이 세포성(細胞性) 면역반응(免疫反應)을 항진(亢進)시키나 체액성(體液性) 면역반응(免疫反應)은 증가(增加)시키지 않으며 내인성(內因性) 및 외인성(外因性) 히스타민 즉시형과민반응(卽時型過敏反應)뿐만 아니라 세포성(細胞性) 면역반응(免疫反應) 조절(調節)에 관여(關與)함을 강력(强力)히 시사(示唆)하는 증거(證據)라고 사료(思料)되었다.

• 대한수의학회지
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• 제24권2호
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• pp.169-171
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• 1984

An expeliment was carried out to measure the cellular immune response in guinea pigs by sensitizing the animals with 2, 4-dinitrochlorobenzene(DNCB). The guinea pigs could be sensitized with one application of DNCB. The sensitizing and challenge dose was standardized. The histological response was characteristic of a delayed hypersensitivity reaction.

• IMMUNE NETWORK
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• 제12권3호
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• pp.118-125
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• 2012

CD40-CD40L-mediated help from CD4 T cells is essential to induce primary CD8 T cell responses specific to the non-inflammatory cell-based antigen H60. In this study, using H60 as a model antigen, we generated recombinant vaccinia viruses (rVVs) expressing the H60 CD8 epitope and investigated whether CD4 help was required to activate the CD8 T cell response specific to the virally expressed H60. The immune response after infection with rVVs expressing H60 was similar to that after immunization with H60 congenic splenocytes, with a peak frequency of H60-specific CD8 T cells detected in the blood on day 10 post-infection. A CD8 T cell response specific for virally derived H60 was not induced in CD4-depleted mice, but was in CD40-deficient mice. These results provide insights into the characterization of the CD8 T cell response specifically for antigens originating from cellular sources compared to viral sources.

• BMB Reports
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• 제49권6호
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• pp.305-310
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• 2016

Toll-like receptors (TLRs) play a critical role in the innate immune response against pathogens. Each TLR recognizes specific pathogen-associated molecular patterns, after which they activate the adaptor protein MyD88 or TRIF-assembled signaling complex to produce immune mediators, including inflammatory cytokines and type I IFNs. Although the activation of TLR is important for host defense, its uncontrolled activation can damage the host. During the past decade, numerous studies have demonstrated that GSK3β is a key regulator of inflammatory cytokine production in MyD88-mediated TLR signaling via TLR2 and TLR4. Recently, GSK3β has also been implicated in the TRIF-dependent signaling pathway via TLR3. In this review, we describe current advances on the regulatory role of GSK3β in immune responses associated with various TLRs. A better understanding of the role of GSK3β in TLR signaling might lead to more effective anti-inflammatory interventions.

• Asian-Australasian Journal of Animal Sciences
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• 제13권1호
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• pp.115-125
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• 2000

In recent years a great deal of information has accumulated for livestock on vitamin. function, metabolism and supplemental needs. The role of the antioxidant "vitamins" (carotenoids, vitamin E and vitamin C) in immunity and health of livestock has been a fruitful area of research. These nutrients play important roles in animal health by inactivating harmful free radicals produced through normal cellular activity and from various stressors. Both in vitro and in vivo studies showed that these antioxidant vitamins generally enhance different aspects of cellular and noncellular immunity. A compromised immune system will result in reduced animal production efficiency through increased susceptibility to diseases, thereby leading to increased animal morbidity and mortality. Vitamin E has been shown to increase performance of feedlot cattle and to increase immune response for ruminant health, including being beneficial for mastitis control. Vitamin E given to finishing cattle at higher than National Research Council (NRC) requirements dramatically maintained the red color (oxymyoglobin) compared with the oxidized metmyoglobin of beef. Under commercial livestock and poultry production conditions, vitamin allowances higher than NRC requirements may be needed to allow optimum performance. Generally, the optimum vitamin supplementation level is the quantity that achieves the best growth rate, feed utilization, health (including immune competency), and provides adequate body reserves.

• Molecules and Cells
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• 제23권1호
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• pp.1-10
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• 2007

Invading pathogens are recognized by diverse germline-encoded pattern-recognition receptors (PRRs) which are distributed in three different cellular compartments: extracellular, membrane, and cytoplasmic. In mammals, the major extracellular PRRs such as complements may first encounter the invading pathogens and opsonize them for clearance by phagocytosis which is mediated by membrane-associated phagocytic receptors including complement receptors. The major membrane-associated PRRs, Toll-like receptors, recognize diverse pathogens and generate inflammatory signals to coordinate innate immune responses and shape adaptive immune responses. Furthemore, certain membrane-associated PRRs such as Dectin-1 can mediate phagocytosis and also induce inflammatory response. When these more forefront detection systems are avoided by the pathogens, cytoplasmic PRRs may play major roles. Cytoplasmic caspase-recruiting domain (CARD) helicases such as retinoic acid-inducible protein I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5), mediate antiviral immunity by inducing the production of type I interferons. Certain members of nucleotide-binding oligomerization domain (NOD)-like receptors such as NALP3 present in the cytosol form inflammasomes to induce inflammatory responses upon ligand recognition. Thus, diverse families of PRRs coordinately mediate immune responses against diverse types of pathogens.