Immune-enhancing effects of a traditional herbal prescription, Kyung-Ok-Ko

노성수,이원화,김경민,나민균,배종섭 대한본초학회 2019 大韓本草學會誌 Vol.34 No.2

Objectives : A traditional herbal prescription, Kyung-Ok-Ko (KOK), has long been used in oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK for immune responses is largely unknown. Based on the above mentioned effects of KOK, other previous reports, and its use in traditional medicine, we hypothesized that KOK displays beneficial effects against methotrexate (MTX)-induced immune suppression. Methods : We investigated the effects of KOK (0.6 g/kg/day, oral (p.o.)) on deteriorated immunity caused by MTX (2 mg/kg/day, p.o.) in an immune suppression mouse model. MTX was fed to mice once a day for 7 days. After the immune responses of the mice deteriorated by MTX treatment, KOK in water was fed to the mice once a day for 14 days. We then measured the expression levels of various cytokines, such as T helper cell (Th1, Th2) cytokines, and the number of immune cells, such as spleen T cells, B cells, and macrophages. Results : The data showed that MTX decreased Th1 profiles (interferon (IFN)-, interleukin (IL)-2, IL-12) and the number of immune cells, and increased Th2 profiles (IL-4, IL-5, IL-13), which were normalized significantly by post-administration of KOK. However, there was no significant difference in body-weight gain between MTX- and KOK-treated mice. Conclusion : These results indicate that KOK has immune-enhancing functions and reduces immunotoxicity of MTX, suggesting that supplementation with KOK will improve immune responses clinically and be useful for the prevention of immune-related diseases.

Immunologic Mechanism of Experimental and Therapeutic Ultraviolet B Responses

Lew, Wook The Korean Association of Immunobiologists 2002 Immune Network Vol.2 No.2

The immunological mechanism of the responses to ultraviolet (UV) B radiation in mouse models were investigated by the suppression of contact hypersensitivity (CHS) and delayed type hypersensitivity (DTH), and susceptibility to infection. However, there are some differences in immune suppression according to the different models as well as the irradiation protocols. Therefore, this review focused on the differences in the suppressive effects on CHS and DTH, and susceptibility to infection in relation to the different in vivo models. Recent advances in cytokine knockout mice experiments have the reexamination of the role of the critical cytokines in UVB-induced immune suppression, which was investigated previously by blocking antibodies. The characteristics of the suppressor cells responsible for UVB-induced tolerance were determined. The subcellular mechanism of UVB-induced immune suppression was also explained by the induction of apoptotic cells through the Fas and Fas-ligand interaction. The phagocytosis of the apoptotic cells is believed to induce the production of the immune suppressive cytokine like interleukin-10 by macrophages. Therefore, the therapeutic UVB response to a skin disease, such as psoriasis, by the depletion of infiltrating T cells could be considered in the extension line of apoptosis and immune suppression.

Immune Enhancement Effects of Codium fragile Anionic Macromolecules Combined with Red Ginseng Extract in Immune-Suppressed Mice

( Ji Eun Kim ),( Chaiwat Monmai ),( Weerawan Rod-in ),( A-yeong Jang ),( Sang-guan You ),( Sang-min Lee ),( Woo Jung Park ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 Journal of microbiology and biotechnology Vol.29 No.9

Codium fragile is an edible seaweed in Asian countries that has been used as a thrombolytic, anticoagulant, antioxidant, anti-inflammatory, and immune-stimulatory agent. Ginseng has also been known to maintain immune homeostasis and to regulate the immune system via enhancing resistance to diseases and microorganisms. In this study, anionic macromolecules extracted from C. fragile (CFAM) were orally administered with red ginseng extract (100 mg/kg body weight) to cyclophosphamide-induced immunosuppressed male BALB/c mice to investigate the immune-enhancing cooperative effect of Codium fragile and red ginseng. Our results showed that supplementing CFAM with red ginseng extract significantly increased spleen index, T- and B-cell proliferation, NK cell activity, and splenic lymphocyte immune-associated gene expression compared to those with red ginseng alone, even though a high concentration of CFAM with red ginseng decreased immune biomarkers. These results suggest that CFAM can be used as a co-stimulant to enhance health and immunity in immunosuppressed conditions.

Polymeric Nanoparticles Containing Both Antigen and Vitamin D3 Induce Antigen-Specific Immune Suppression

정호현,김상현,문준혁,정성운,장선동,박찬수,이종길 대한면역학회 2019 Immune Network Vol.19 No.3

The active form of vitamin D3, 1,25-dihydroxyvitamin D3 (aVD3), is known to exert beneficial effects in the treatment of autoimmune diseases because of its immunosuppressive effects. However, clinical application of aVD3 remains limited because of the potential side effects, particularly hypercalcemia. Encapsulation of aVD3 within biodegradable nanoparticles (NPs) would enhance the delivery of aVD3 to antigen presenting cells, while preventing the potential systemic side effects of aVD3. In the present study, polymeric NPs containing ovalbumin (OVA) and aVD3 (NP[OVA+aVD3]) were prepared via the water-in-oil-in-water double emulsion solvent evaporation method, after which their immunomodulatory effects were examined. Bone marrow-derived immature dendritic cells (DCs) treated with NP(OVA+aVD3) did not mature into immunogenic DCs but were converted into tolerogenic DCs, which express low levels of co-stimulatory molecules and MHC class II molecules, produce lower levels of pro-inflammatory cytokines while increasing the production of IL-10 and TGF-β, and induce the generation of Tregs. Intravenous injection with NP(OVA+aVD3) markedly suppressed the generation of OVA-specific CTLs in mice. Furthermore, OVA-specific immune tolerance was induced in mice orally administered with NP(OVA+aVD3). These results show that biodegradable NPs encapsulating both antigen and aVD3 can effectively induce antigen-specific immune suppression.

수태중인 생쥐에 있어서 림프구아형 및 자연살해세포 활성도의 변화

신주옥(Chuog Shin),고기석(Ki-Seok Koh),최임순(Rim-Soon Choe) 대한의생명과학회 1996 Biomedical Science Letters Vol.2 No.2

수태기간중 태아가 모체에 의해 면역학적으로 거부반응을 일으키지 않고 동종이식 상태로 유지되는 기작을 밝히는 연구의 일환으로 C3H/HeJ계의 암컷 생쥐와 DBA/2계의 수컷 생쥐를 교배하여 모체에서 발생되는 체계적인 면역기능 및 국소적 면역기능현상에 대하여 연구하고자 수태기간별로 비장 및 자궁으로 들어가는 림프절에서 T세포 및 B세포의 아형을 측정하였고 자연살해세포의 활성도를 측정하였다. 또한 수태혈청 및 수태성 호르몬이 자연살해세포의 활성도에 미치는 영향을 알아보았다. 각 수태기간별로 비장세포에 있어서 T세포와 B세포의 아형을 관찰한 결과, Thy-1.2?세포는 수태기간중 중기 이후에 감소하기 시작하여 수태 4기에는 대조군에 비하여 유의하게 감소하였으며 수태말기에는 회복하였다. L3T4?세포도 Thy-1.2? 세포와 비교하여 비슷한 경향으로 감소 또는 증가하였다. Ly2?세포는 수태중기 이후부터 대조군에 비하여 유의하게 증가하였으며, B세포는 수태중기 이후부터 수태말기까지 계속 증가하였다. 비장에 있어서 자연살해세포의 세포독성은 수태 5일에서 수태 8일사이에 가장 증가하였으며 그 이후는 대조군 수준으로 감소하였다. 정상혈청 및 수태혈청의 자연살해세포의 세포독성에 대한 영향을 수태시기별로 조사한 결과, 정상혈청과 수태혈청 모두 자연살해세포의 세포독성을 유의하게 억제하였으며, Progesterone은 시험관내 실험과 생채내 실험 모두 약리적인 농도이상에서 농도에 의존적으로 자연잘해세포의 세포독성을 증가시켰으며, HCG는 5 unit/㎖에서 5000 unit/㎖까지 처리농도에 비례하여 자연살해세포의 세포독성을 억제하였다. 자궁으로 들어가는 림프절에서 T세포의 아형은 Thy-1.2?세포는 수태 2기부터 증가하여 대조군보다 유의하게 증가하였으며, L3T4?세포의 유의한 변화없이 Ly2?세포가 수태 2기 이후부터 대조군에 비하여 유의하게 증가하였고 분만 직전에는 조금 감소하였다. 자궁으로 들어가는 림프절에서의 자연살해세포의 세포독성은 착상직후 대조군에 비하여 유의하게 증가하였으며, 수태중기와 수태후기에도 대조군에 비하여 세포독성이 증가하였으며, 같은 시기의 비장세포의 자연살해세포의 세포독성보다 높게 나타났다. The conceptus which are resulted by mating between two genetically non-identical partners can be considered to be an allograft to the mother science which is not rejected by the mother's immunological attack. The present studies have been, therefore, attempted in order to elucidate the mechanism by which protection of the feto-placental allograft, between the C3H/HeJ female mouse and DBA/2 male mouse occurred. For this purpose, firstly systemic immunity was investigated by measuring T and B lymphocytes subsets. Natural killer cell activity in maternal splenic tissue and by observing the effects of pregnancy serums, progesterone and hCG on immune systems. Secondly, local immunity also investigated by measuring T lymphocytes subsets, natural killer cell activity in lymph nodes draining the uterus. The subsets of Thy-1.2? cells and L3T4? cells decreased slightly while the subsets of Ly2? cell increased significantly compared with those of the control group beyond the mid-gestational stage. The subsets of B cell gradually increased from the mid-gestational stage untill delivery. The natural killer cell activity in the maternal splenic tissue significantly increased during the period of 5th to 8th day of gestation. The natural killer cell activity was significantly suppressed by the pregnancy serums and non-pregnant serums compared with those of serum-free group. The treatment of hCG significantly suppressed natual killer cell activity in the dose dependent manner (1 unit/㎖-1000 unit/㎖) while progesterone increased the natural killer cell activity at phamarcological dose only. In the lymph nodes draining the uterus, the subsets of Thy-1.2? cells significantly increased during the period of implantation and L3T4? cell subsets slightly increased during the mid-gestational stage. The subsets of Ly2? cell increased significantly during the mid-gestational stage, but decreasing slightly before delivery. The natural killer cell activity was significantly elevated after the implantation period in the lymph nodes draining the uterus. The natural killer cell activity of the lymph nodes draining the uterus was higher than those of splenic tissue during the same periods of gestation. It is therefore, concluded that during the pregnancy, the phenomena which the feto-placental allograft has not been rejected and rather protected from the maternal immunological attack might be due to local immune suppression in feto-maternal interface tissues rather than systemic immune suppression. And the subsets of Thy-1.2? cells and L3T4? cells mainly contribute to accepting allograft in early stage of pregnancy, while the subsets of Ly2? cell and the subsets of B cell increased significantly compared with those of the control group beyond the mid-gestational stage, so their role in systemic immunity and local immunity gradually increased from the mid-gestational stage untill delivery.

전신면역억제를 지속한 각막윤부이식술 수여안의 중기 임상결과

한의석,인연석,위원량,이진학,김미금,Eui Seok Han Youn Seok In Won Ryang Wee Jin Hak Lee Mee Kum Kim 대한안과학회 2007 대한안과학회지 Vol.48 No.2

Purpose: To investigate the midterm outcome of limbal transplantation combined with continuous systemic immune suppression. Methods: The medical records of 15 eyes in 14 patients who underwent limbal transplantation were reviewed retrospectively. All had been followed up for 6 months or more. Limbal transplantation was performed with 360 degrees of 0.19 mm partial corneal trephined tissues, accompanied with transient amniotic membrane transplantation. The procedure was accomplished with systemic cyclosporine or mycophenolate. We defined complete success as neither rejection nor epithelial defect; partial success as partial conjunctival ingrowth and neovascularization without epithelial defect; and graft failure as persistent epithelial defect or total conunctivalization with neovascularization. Results: Mean age at surgery was 45.1 years. 9 eyes yielded complete success, 2 had partial success, and graft failure occurred in 4 on an average of 23.4 months postoperatively. Success including complete and partial success showed 67% incidence (4 of 6) of chemical burn, 33% (1 of 3) with Stevens-Johnson syndrome, and 100% (6 of 6) experienced another intractable ocular surface disease. Of 10 eyes (67%), which experienced graft rejection in an average of 2.7 months; 4 demonstrated full recovery with oral corticosteroid and enhanced immunosuppression, 2 presented with chronic graft rejection, and the other 4 ended in graft failure. Conclusions: Total success rate was revealed as 73.3% for on average 23.4 months in limbal transplantation with continuous systemic immune suppression, utilized for chronic intractable ocular surface disease.

Neprilysin-1 in Cotesia plutellae Suppresses Nodule Formation in Hemolymph of Plutella xylostella (L.)

Wook Hyun Cha,Dae-Weon Lee 한국응용곤충학회 2015 한국응용곤충학회 학술대회논문집 Vol.2015 No.10

One of the endoparasitoid wasp, Cotesia plutellae (Braconidae), parasitizes young larvae of the diamondback moth, Plutella xylostella. For the successful parasitization, C. plutellae required suppression of immune response in P. xylostella. Maternal (polydnavirus, venom proteins and ovary proteins) and embryonic (teratocytes) factors have been involved in immune-suppression. In this study, we performed transcriptome analysis of venom of C. plutellae and identify neprilysin-1 (Cp-NEP1) as a potential immunosuppressive protein. Cp-NEP1 encoded 451 amino acids and largely belongs to the hymeopteran neprilysin family via phylogenetic analysis. It is of interest that Cp-NEP1 has no conserved motifs such as zinc-binding domain (HExxH), substate binding domain (NAYY/F) and protein folding and maturation domain (CxxW) generally identified in other neprilysin family. In order to examine the biochemical function of Cp-NEP1, the recombinant Cp-NEP1 tagged with N-terminally 6X His was constructed and expressed in Escherichia coli. Expression of Cp-NEP1 was confirmed with SDS-PAGE and peptide sequencing. Recombinant Cp-NEP1 significantly suppressed nodule formation when the co-injection with E. coli. These results suggest that Cp-NEP1 contributes to suppression of immune response in P. xylostella and that the conserved motifs reported from other neprilysin do not involve immunosupperssion.

Original Articles : Dietary turmeric presents mild immune suppressing and anti-inflammatory effects

( Yun Mi Kim ),( Jin A Lee ),( Tae Hoon Kim ),( Bock Gie Jung ),이봉주 ( Bong Joo Lee ) 한국예방수의학회 2014 예방수의학회지 Vol.38 No.1

Pathologic chronic inflammation, such as that seen with microbial infection and autoimmune diseases, creates microenvironmental conditions that promote cancer. Therefore, if chronic inflammation can be alleviated, the risk of carcinogenesis may decrease. Turmeric is a dried rhizome powder from Curcuma longa. Curcumin, the major constituent of turmeric, presents anti-inflammatory, antioxidant, antimicrobial, and chemopreventive activities. In the present study, we investigated immune responses to dietary turmeric in ICR mice to determine the effects of turmeric when used as a dietary chemoprevention agent. After dietary turmeric was given for three or six weeks to ICR male mice, the immune responses were characterized. The methods of characterization involved; the determination of the T cell subpopulation in the spleen, relative mRNA expression levels of IFN-γ and TNF-α, and serum lysozyme activity. Dietary turmeric was found to decrease spleen weight, decrease the proportion of CD4-CD8+ T cells, and decrease phagocytic activity. These results suggest that turmeric might alleviate abnormal chronic inflammation by the action of immune suppression.

Crosstalk between angiogenesis and immune regulation in the tumor microenvironment

Hei Jung Kim,Young Rae Ji,You Mie Lee 대한약학회 2022 Archives of Pharmacal Research Vol.45 No.6

Cancer creates a complex tumor microenvironment(TME) composed of immune cells, stromal cells,blood vessels, and various other cellular and extracellularelements. It is essential for the development of anti-cancercombination therapies to understand and overcome thishigh heterogeneity and complexity as well as the dynamicinteractions between them within the TME. Recent treatmentstrategies incorporating immune-checkpoint inhibitorsand anti-angiogenic agents have brought many changes andadvances in clinical cancer treatment. However, there arestill challenges for immune suppressive tumors, which arecharacterized by a lack of T cell infi ltration and treatmentresistance. In this review, we will investigate the crosstalkbetween immunity and angiogenesis in the TME. In addition,we will look at strategies designed to enhance anti-cancerimmunity, to convert “immune suppressive tumors” into“immune activating tumors,” and the mechanisms by whichthese strategies enhance eff ector immune cell infi ltration.

수태중인 생쥐에 있어서 림프구아형 및 자연살해세포 활성도의 변화

최임순,고기석,신주옥 THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCIEN 1996 Journal of biomedical laboratory sciences Vol.2 No.2

수태기간중 태아가 모체에 의해 면역학적으로 거부반응을 일으키지 않고 동종이식 상태로 유지되는 기작을 밝히는 연구의 일환으로 C3H/HeJ계의 암컷 생쥐와 DBA/2계의 수컷 생쥐를 교배하여 모체에서 발생되는 체계적인 면역기능 및 국소적 면역기능현상에 대하여 연구하고자 수태기간별로 비장 및 자궁으로 들어가는 림프절에서 T세포 및 B세포의 아형을 측정하였고 자연살해 세포의 활성도를 측정하였다. 또한 수태혈청 및 수태성 호르몬이 자연살해세포의 활성도에 미치는 영향을 알아보았다. 각 수태기간별로 비장세포에 있어서 T세포와 B세포의 아형을 관찰한 결과, Thy-1.2+ 세포는 수태기간중 중기 이후에 감소하기 시작하여 수태 4기에는 대조군에 비하여 유의하게 감소하였으며 수태말기에는 회복하였다. L3T4+ 세포도 Thy-1.2+ 세포와 비교하여 비슷한 경향으로 감소 또는 증가하였다. Ly2+ 세포는 수태중기 이후부터 대조군에 비하여 유의하게 증가하였으며, B세포는 수태중기 이후부터 수태말기까지 계속 증가하였다. 비장에 있어서 자연살해세포의 세포독성은 수태 5일에서 수태 8일사이에 가장 증가하였으며 그 이후는 대조군 수준으로 감소하였다. 정상혈청 및 수태혈청의 자연살해세포의 세포독성에 대한 영향을 수태시기별로 조사한 결과, 정상혈청과 수태혈청 모두 자연살해세포의 세포독성을 유의하게 억제하였으며, Progesterone은 시험관 내 실험과 생체내 실험 모두 약리적인 농도이상에서 농도에 의존적으로 자연살해세포의 세포독성을 증가시켰으며, HCG는 5 unit/ml에서 5000 unit/ml까지 처리농도에 비례하여 자연살해세포의 세포독성을 억제하였다. 자궁으로 들어가는 림프절에서 T세포의 아형은 Thy-1.2+ 세포는 수태 2기부터 증가하여 대조군보다 유의하게 증가하였으며, L3T4+ 세포의 유의한 변화없이 Ly2+ 세포가 수태 2기 이후부터 대조군에 비하여 유의하게 증가하였고 분만 직전에는 조금 감소하였다. 자궁으로 들어가는 림프절에서의 자연살해세포의 세포독성은 착상직후 대조군에 비하여 유의하게 증가하였으며, 수태중기와 수태후기에도 대조군에 비하여 세포독성이 증가하였으며, 같은시기의 비장세포의 자연살해세포의 세포독성보다 높게 나타났다. The conceptus which are resulted by mating between two genetically non-identical partners can be considered to be an allograft to the mother science which is not rejected by the mother's immunological attack. The present studies have been, therefore, attempted in order to elucidate the mechanism by which protection of the feto-placental allograft, between the C3H/HeJ female mouse and DBA/2 male mouse occurred. For this purpose, firstly systemic immunity was investigated by measuring T and B lymphocytes subsets. Natural killer cell activity in maternal splenic tissue and by observing the effects of pregnancy serums, progesterone and hCG on immune systems. Secondly, local immunity also investigated by measuring T lymphocytes subsets, natural killer cell activity in lymph nodes draining the uterus. The subsets of Thy-1.2+. cells and L3T4+ cells decreased slightly while the subsets of Ly2+ cell increased significantly compared with those of the control group beyond the mid-gestational stage. The subsets of B cell gradually in-creased from the mid-gestational stage untill delivery. The natural killer cell activity in the maternal splenic tissue significantly increased during the period of 5th to 8th day of gestation. The natural killer cell activity was significantly suppressed by the pregnancy serums and non-pregnant serums compared with those of serum-free group. The treatment of hCG significantly suppressed natual killer cell activity in the dose dependent manner (1 unit/ml-1000 unit/ml) while progesterone increased the natural killer cell activity at phamarcological dose only. In the lymph nodes draining the uterus, the subsets of Thy-1.2+ cells significantly increased during the period of implantation and L3T4+ cell subsets slightly increased during the mid-gestational stage. The subsets of Ly2+ cell increased significantly during the mid-gestational stage, but decreasing slightly before delivery. The natural killer cell activity was significantly elevated after the implantation period in the lymph nodes draining the uterus. The natural killer cell activity of the lymph nodes draining the uterus was higher than those of splenic tissue during the same periods of gestation. It is therefore, concluded that during the pregnancy, the phenomena which the feto -placental allograft has not been rejected and rather protected from the maternal immunological attack might be due to local immune suppression in feto-maternal interface tissues rather than systemic immune suppression. And the subsets of Thy-1.2+ cells and L3T4+ cells mainly contribute to accepting allograft in early stage of pregnancy, while the subsets of Ly2+ cell and the subsets of B cell increased significantly compared with those of the control group beyond the mid-gestational stage, so their role in systemic immunity and local immunity gradually increased from the midgestational stage untill delivery.