• Biomolecules & Therapeutics
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• 제19권1호
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• pp.77-83
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• 2011

Sulforaphane is an isothiocyanate found in cruciferous vegetables that has been reported to be an effective cancer preventive agent inducing growth arrest and/or cell death in cancer cells of various organs. This paper reports that sulforaphane exerts immunomodulatory activity on the MHC-restricted antigen presenting function. Sulforaphane efficiently increased the class II-restricted presentation of an exogenous antigen, ovalbumin (OVA), in both dendritic cells (DCs) and peritoneal macrophages in vitro. The class II-restricted OVA presentation-enhancing activity of sulforaphane was also confirmed using mice that had been injected with sulforaphane followed by soluble OVA. On the other hand, sulforaphane did not affect the class I-restricted presentation of exogenous OVA at concentrations that increase the class II-restricted antigen presentation. At a high concentration ($20\;{\mu}M$), sulforaphane inhibited the class I-restricted presentation of exogenous OVA. Sulforaphane did not affect the phagocytic activity of the DCs, and the cell surface expression of total H-$2K^b$, B7-1, B7-2 and CD54 molecules, even though it increased the expression of I-$A^b$ molecules to a barely discernable level. These results show that sulforaphane increases the class II-restricted antigen presenting function preferentially, and might provide a novel insight into the mechanisms of the anti-cancer effects of sulforaphane.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.35-41
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• 2013

Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.

• 한국식품영양과학회지
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• 제29권3호
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• pp.466-470
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• 2000

본 연구는 절식 및 재급여가 Sprague-Dawley계통 수컷 흰쥐(55마리)의 지방조직내 LPL활성과 지방합성량에 미치는 영향을 구명하였다. 아울러 재급여하는 동안 다양한 식이섭취 제한이 LPL활설과 지방홥성에 어떻게 영향을 미치는 지도 조사하였다. 대조군(5마리)은 무제한 식이를 급여하였으며 실험 첫날 식이섭취 상태에서 바로 희생시켰으며, 그 외 모든 쥐는 2일간 절식시켰다. 2일 절식 후 그중 5마리의 주를 희생하여 절식군으로 두었으며, 나머지 쥐(45마리)는 절식 후 식이를 재급여하였는데, 이때 재급여하는 동안 식이섭취 제한 효과를 보기 위해 adlibitum group, 20% food restricted group(ad libitum group의 80%) 및 40% food restricted group(ad libitum group의 60%)로 나누어 실시하였다. 재급여 후 7일, 14일 및 21일째 되는 날 각각 희생하였다. 지방조직의 지방함성은 포도당이 총 지방이므로 변한 양으로 측정하였다. 체중과 지방조직의 무게는 재급여 후 ad libitum group은 5일만에, 20% food restricted group은 14일만에 대조군 수준에 도달하였다. 재급여시 40% food restricted group의 체중과 지방조직의 무게는 재급여 후 21일째가 되도록 대조군 수준에 도달하지 못했다. 식이 재급여 후 21일째 ad libitum group의 혈청 총 콜레스테롤함량은 대조군에 비해 높았다(p<0.05). HDL-콜레스테롤함량은 재급여시 40% food restricted group가 대조군에 비해 높았다 (p<0.05). 그러나 HDL-C/TC비율과 중성지방함량은 처리군간에 유의적인 변화를 나타내지 않았다. 절식 후 지방조직내 지방합성량과 LPL(HR-LPL과 TE-LPL)활성은 대조군에 비해 현저히 저하되었다(p<0.05). 재급여 후 21일째 ad libitum group의 지방합성량은 대조군에 비해 낮았다(p<0.05). 그러나 40% food restricted group의 지방합성량은 대조군에 비해 높았다(p<0.05). HR-LPL과 TE-LPL활성은 재급여시ad libitum group과 20% food re-stricted group은 재급여 후 21일째가 되도록 대조군수준에 도달하지 못했다. 이러한 결과를 통해 절식 후 식이를 재급여할 경우 식이섭취 제한은 LPL활성이 증가되는 것을 부분적으로 혹은 완전히 예방할 수 있으며, 지방조직내 지방축적에 영향을 미친다는 것을 말해 준다.

• IMMUNE NETWORK
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• 제7권4호
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• pp.197-202
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• 2007

Background: Immunomodulators enhancing MHC-restricted antigen presentation would affect many cellular immune reactions mediated by T cells or T cell products. However, modulation of MHC-restricted antigen presentation has received little attention as a target for therapeutic immunoregulation. Here, we report that lectins isolated from mushroom Fomitella fraxinea enhance MHC-restricted exogenous antigen presentation in professional antigen presenting cells (APCs). Methods: Lectins, termed FFrL, were isolated from the carpophores of Fomitella fraxinea, and its effects on the class I and class II MHC-restricted presentation of exogenous ovalbumin (OVA) were examined in mouse dendritic cells (DCs) and mouse peritoneal macrophages. The effects of FFrL on the expression of total MHC molecules and the phagocytic activity were also examined in mouse DCs. Results: DCs cultured in the presence of FFrL overnight exhibited enhanced capacity in presenting exogenous OVA in association with class I and class II MHC molecules. FFrL increased slightly the total expression levels of both class I (H-$2K^b$) and class II (I-$A^b$) MHC molecules and the phagocytic activity of DCs. Antigen presentation-enhancing activity of FFrL was also observed in macrophages isolated from mouse peritoneum. Conclusion: Lectins isolated from the carpophores of Fomitella fraxinea increase MHC-restricted exogenous antigen presentation by enhancing intracellular processing events of phagocytosed antigens.

• IMMUNE NETWORK
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• 제11권6호
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• pp.412-415
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• 2011

Hypocrellin A has gained much attention in recent years due to its light-induced antitumor, antifungal and antiviral activities. Here we report that hypocrellin A exerts immunomodulatory effects on MHC-restricted presentation of antigen. Hypocrellin A inhibited class II-MHC restricted presentation of exogenous antigen, but not class I MHC-restricted presentation of exogenous antigen, in dendritic cells. Hypocrellin A also inhibited the cytosolic pathway of endogenous antigen presentation. However, hypocrellin A did not inhibit the expression of class I and class II MHC molecules on dendritic cells (DCs), the phagocytic activity of DCs, or the $H-2K^b$-restricted presentation of a synthetic peptide, SIINFEKL. These results show that hypocrellin A differentially modulates the MHC-restricted antigen presentation pathways.

• Asian-Australasian Journal of Animal Sciences
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• 제32권9호
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• pp.1469-1474
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• 2019

Objective: Physical activity restriction in sows may lead to behavioral abnormalities and affective disorders. However, the psychophysiological state of these sows is still unclear. As miRNAs can be used as effective markers of psychopathy, the present study aimed to assess the difference in microRNA expression between the long-term activity restricted sows and activity free sows, thus contributing to the understanding of abnormal sow behavior. Methods: Four dry sows (sixth parity, Large${\times}$White genetic line) were selected from activity restricted crates (RC) or activity free pens (FP) separately. microRNAs in the ventromedial prefrontal cortex (vMPFC) and serum were examined using real-time polymerase chain reaction, and the correlation between the miRNAs expressed in the vMPFC and serum was evaluated. Results: miR-134 (1.11 vs 0.84) and miR-1202 (1.09 vs 0.85) levels were higher in the vMPFC of the RC sows than in the FP sows (p<0.01). Furthermore, miR-132 (1.27 vs 1.08) and miR-335 (1.03 vs 0.84) levels were also higher in the RC sows than in FP sows (p<0.05); however, miR-135a, miR-135b, miR-16, and miR-124 levels were not different (p>0.05). The relative expression of serum miR-1202 was higher in the RC sows than in the FP sows (1.04 vs 0.54) (p<0.05), and there was a strong correlation (R = 0.757, p<0.05) between vMPFC and Serum levels of miR-1202. However, no significant difference was observed in miR-16 levels in the serum of the RC sows and FP sows (p>0.05). Conclusion: This pilot study demonstrates that long-term activity restriction in sows likely results in autism or other complex psychopathies with depression-like behaviors. These observations may provide new insights for future studies on abnormal behavior in sows and contribute to research on human psychopathy.

• Natural Product Sciences
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• 제19권4호
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• pp.347-354
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• 2013

Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. However, the therapeutic mechanism has not yet been elucidated. In this study, we examined the effects of cordycepin on the antigen-presenting function of antigen-presenting cells (APCs). Dendritic cells (DCs) were cultured in the presence of cordycepin and then allowed to phagocytose microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using CD8 and CD4 T cells. Also, we confirmed the protein levels of proinflammatory cytokines through RT-PCR and Western blot analysis. Cordycepin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of cordycepin was also confirmed using mice that had been injected with cordycepin followed by soluble OVA. Furthermore, cordycepin suppressed the mRNA and protein levels of iNOS, COX-2, pro-inflammatory cytokines in a concentration-dependent manner. These results provide an understanding of the mechanism of the T cell response-regulating activity of cordycepin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.

• IMMUNE NETWORK
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• 제14권6호
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• pp.328-332
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• 2014

Dexamethasone (Dex) was shown to inhibit the differentiation, maturation, and antigen-presenting function of dendritic cells (DC) when added during DC generation or maturation stages. Here, we examined the direct effects of Dex on MHC-restricted antigen processing. Macrophages were incubated with microencapsulated ovalbumin (OVA) in the presence of different concentrations of Dex for 2 h, and the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Dex inhibited both class I- and class II-restricted presentation of OVA to T cells; this inhibitory effect on antigen presentation was much more potent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVA peptide SIINFEKL was not blocked by Dex. In addition, short-term treatment of macrophages with Dex had no discernible effects on the phagocytic activity, total expression levels of MHC molecules or co-stimulatory molecules. These results demonstrate that Dex inhibits intracellular processing events of phagocytosed antigens in macrophages.

• Journal of Nutrition and Health
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• 제24권3호
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• pp.149-156
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• 1991

고지방식이와 총열량섭취 제한식이가 protein kinase C 활성에 미치는 영향을 규명하고자 기타 양양소 또 총열량섭취가 정확이 조절된 식이를 제조하여 투여해본 결과, protein kinase C의 활성은 본 실험에서 사용한 옥수수유의 양의 증가에 따라 cytosolic과 membrane-associated protein kinase C의 활성을 모두 증가시키는 것을 관찰 하였다. 또한 기타 영양소는 같게 투여하고 열량소만 40% 감소시킨 실험군은 대조군에 비해 양쪽의 protein kinase C가 모두 감소하는 경향을 보였다.

• Asian-Australasian Journal of Animal Sciences
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• 제26권12호
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• pp.1717-1725
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• 2013

The objectives of this study were to compare visual observation and an electronic grazing time method and to evaluate the effects of nutritional plans on intake, grazing behavior and horizontal and vertical locomotion of young bulls in a tropical pasture. Thirty-nine Nellore young bulls with an average body weight of $345{\pm}9.3$ kg kept in pasture were used. The experimental treatments consisted of: restricted: animals kept in a plot with a low mass of forage receiving mineral mixture only; control: animals receiving mineral mixture only; HPHC: a high protein and high carbohydrate supplement; HPLC: a high protein and low carbohydrate supplement; LPHC: a low protein and high carbohydrate supplement; LPLC: a low protein and low carbohydrate supplement. GPS collars equipped with activity sensors were used. Information about head position, latitude, longitude and altitude were recorded. Daytime grazing behavioral patterns monitored by a continuous focal animal recording method was compared to behavior estimated by the activity sensor. Feed intake was estimated by a marker method. The Restricted group presented lower (p<0.05) intake of dry matter and TDN. However, difference in dry matter intake was not found (p>0.05) between non-supplemented and supplemented animals. Difference was not found (p>0.05) in daytime grazing time obtained by visual observation or the activity sensor method. The restricted group showed longer (p<0.05) grazing time (9.58 h/d) than other groups, but difference was not found (p>0.05) in the grazing time between Control (8.35 h/d) and supplemented animals (8.03 h/d). The Restricted group presented lower (p<0.05) horizontal locomotion distance (2,168 m/d) in comparison to other groups (2,580.6 m/d). It can be concluded that the use of activity sensor methods can be recommended due to their being similar to visual observation and able to record 24-h/d. While supplements with high carbohydrates reduce pasture intake, they do not change grazing behavior. Moderate supplementation (until 50% of protein requirement and 30% of energy requirement) of beef cattle on tropical pasture has no effect on daily locomotion.