• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.388-394
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• 2009

The cytokines which is produced by allergen-specific T helper (Th) cells play a pivotal role in the pathogenesis of asthma. Asthma is caused by exaggerated T-helper 2 (Th2)-based immune responses. It is suggested that controlling such Th2-based response is necessary for asthma therapy. The current therapies for asthma focus primarily on control of symptoms and suppression of inflammation, without affecting the underlying cause. So, we examined that anti-asthmatic drugs might have play a certain role in Th2/Th1 balance. Splenocytes isolated from ovalbumin (OVA)-sensitized mice cultured with anti-asthmatic drugs. It is well known that Th2 and Th1 immune responses can balance one another, as Th2 mediators suppress Th1 responses and Th1 mediators similarly inhibit Th2 responses. But salmeterol inhibits both of Th1 and Th2 mediators, which salmeterol is a suppressor of immune responses not only a suppressor of Th2-based immune responses. Aminophylline is a weak suppressor of immune responses. But ipratropium and cromoglycate don't have any suppressor effect to Th2-driven responses. They only have suppressor effect to Th1 immune responses. Salmeterol, ipratropium, aminophylline, and cromoglycate augmented mRNA levels of CRTH2, EP2, and IP2 receptors in OVA-sensitized splenocytes. It is well known that the up-regulation of CRTH2 - $PGD_2$ receptor - results in restraint of eosinophil recruitment and that the increment of IP and EP2 - $PGI_2$ and $PGE_2$ receptor, respectively - may induce the accumulation of cAMP that decrease the effector function of T cells. Moreover salmeterol and cromoglycate increase the mRNA expression of $PGD_2$ synthase. These findings indicate that anti-asthma agents may alleviate the immunological responses that cause the asthmatic diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5181-5186
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• 2014

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

• Microbiology and Biotechnology Letters
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• v.35 no.2
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• pp.118-127
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• 2007

Germanium-fortified yeast (GY) is a organic germanium-fortified yeast with potent immune modulating activities including anti-inflammatory effect. Through cell line studies, we observed that GY can modulate the diverse immune activity but little evidence was provided on the mechanism of GY in modulating immune activities in other higher animals. In this study, we investigated the effect of GY on modulation of immune function in mice. GY was administered in normal mice or tumor-bearing mice and then effect of GY on modulation of host immune system was analyzed by using ex vivo isolated macrophages, B cells, NK cells. Admistration of GY in mice induced macrophage activation thereby increased effector function of macrophage such as increased phagocytosis, chemotaxis, adherence, $O_2-release$, NO, $TNF-{\alpha}$ production. In addition, GY administration Increased B lymphocyte activation and plaque forming cells. Furthermore, GY administration increased NK-cell mediated cytotoxicity. Furthermore, GY administration suppressed progression of tumor in mice by increasing $TNF-{\alpha}$ production and effector function of NK cells. Our results showed that GY has a potent immunostimulatory function in vivo mice model. Proper modulation and administration of GY in human could be helpful to maintaining immunological homeostasis by modulating host immune system.

• IMMUNE NETWORK
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• v.2 no.2
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• pp.109-114
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• 2002

Background: To investigate the role of sympathetic nervous system (SNS) in moxibustion-induced immunomodulation, the effects of chemical sympathectomy on moxibustion-induced changes in splenic NK cell cytotoxicity, T and B cell proliferation were studied in Sprague-Dawley male rats. Methods: Chemical sympathectomy was achieved with intraperitoneal injection of 6-hydroxydopamine 50 mg/kg/day for 3 successive days. Direct moxibustion (6-minute interval, 9 moxa ball, each of which weighing 0.007 g and burning for 40 seconds) was applied on unilateral anterior tibial muscle region where Zusanli (ST36) acupoint is located, once a day for 7 successive days. NK cell cytotoxicity was measured by $4hr-^{51}Cr$ release assay. Mitogen-induced lymphocyte proliferation was analyzed by [$^3H$]-thymidine incorporation assay. Results: NK cell cytotoxicity was suppressed by moxibustion, more in sympathectomized rats than in vehicle-treated rats. T cell proliferation induced by concanavalin A was not affected by moxibustion. B cell proliferation induced by lipopolysaccharide showed no significant change in vehicle-treated rats, but an increase in sympathectomized rats by moxibustion. Sympathectomy alone induced augmentation of NK cell cytotoxicity and suppression of T cell proliferation. Conclusion: These results suggest that SNS has no direct relation with moxibution-induced immunomodulation but has an important role in the mechanism to keep the homeostasis of immune system by tonically inhibiting excessive changes of various immune components.

• Journal of fish pathology
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• v.23 no.1
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• pp.9-16
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• 2010

We determined the effects of temperature shifts on the kinetics of the numbers of antibody-secreting cell (ASC) in the olive flounder Paralichthys olivaceus immunised with formalin-killed Edwardsiella tarda. When fish that were acclimated to $22^{\circ}C$ and immunised at that temperature were transferred to a lower temperature ($12^{\circ}C$) at a various times (immediately, 1, 2 or 4 weeks) after immunisation, both further differentiation of B cells and secretion of antibody from the ASC developed at $22^{\circ}C$ were suppressed at $12^{\circ}C$. However, in the converse experiment ($12^{\circ}C$ to $22^{\circ}C$), the magnitude of the humoral immune response was recovered independent of the time of the transfer after immunisation at low temperature, even though the peak levels of each transferred group did not reach the level found in $22^{\circ}C$ control group. The results were confirmed by counting the number of specific antibody secreting cells (SASC) in the spleen. This study provides the evidences of the immune reaction that the potential for antibody production in B cells of flounder, the most important species in aquatic industry of Korea, immunized at high temperature is suppressed by subsequent exposure to low temperature and that low temperature-induced humoral immuno suppression can be reversed by exposure to a higher temperature.

• Asian-Australasian Journal of Animal Sciences
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• v.14 no.1
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• pp.21-29
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• 2001

An experiment was conducted with twenty crossbred male lambs to assess the effect of cotton (Gossypium) seed meal (CSM) on blood constituents and immunity. Lambs were randomly assigned to a reference diet (30% deoiled peanut meal, DPNM) and four test diets containing 40% of either raw, 45 minutes cooked, 1% $Ca(OH)_2$ and iron (1 free gossy-pol, FG : 0.3 Fe) treated CSM (replacing approximately 50%, reference concentrate mixture). These isonitrogenous and isocaloric concentrate mixtures were fed to meet 80% of protein requirements (NRC, 1985) along with ad lib maize hay for 180 days. Blood was collected at 60, 120 and 180 days post feeding. The lambs were sensitized with Brucella abortus S99 antigen after 140 days and were subjected to ELISA and delayed type hypersensitivity. Blood haemoglobin, erythrocyte count, leucocyte count, total protein, total albumin, total globulin, urea, creatinine concentration and aspartate aminotransferase activity in lambs fed on raw or processed CSM were comparable to the values of reference lambs. The higher (p<0.01) blood glucose levels observed in CSM fed lambs at 60 days of feeding was latter reduced to the levels comparable with those on reference diet at 120 and 180 days of feeding. The alanine amino transferase activity was lower in lambs fed raw and cooked CSM containing diets at 120 and 180 days of feeding. A marginal increase in serum iron and alkaline posphatase activity was observed in iron treated group and raw CSM fed lambs, respectively. The humoral immune response and DTH reactivity was lower (p<0.05) in lambs fed raw CSM (consuming 302.83 mg FG/day). Cooking, $Ca(OH)_2$ and iron treatment of raw CSM showed a positive response in alleviating the suppression of immune response owing to the reduced consumption of FG by 40.19, 17.40% and 26.73%, respectively in these diets. The present study thus indicated that consumption of 40% raw CSM (302.83 mg FG/day) though did not affect majority of the haematological and blood biochemical parameters, but markedly suppressed the immune mechanism of lambs.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2943-2948
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• 2012

Arsenic exposure is a serious health hazard worldwide. We have previously established that it may result in immune suppression by upregulating Th2 cytokines while downregulating Th1 cytokines and causing lymphocytic death. Treatment modalities for arsenic poisoning have mainly been restricted to the use of chelating agents in the past. Only recently have combination therapies using a chelating agent in conjunction with other compounds such as anti-oxidants, micronutrients and various plant products, been introduced. In the present study, we used T11TS, a novel immune potentiating glycopeptide alone and in combination with the sulfhydryl-containing chelator, mono-iso-amyl-dimarcaptosuccinic acid (MiADMSA) as a therapeutic regimen to combat arsenic toxicity in a mouse model. Results indicated that Th1 cytokines such as TNF-${\alpha}$, $IFN{\gamma}$, IL12 and the Th2 cytokines such as IL4, IL6, IL10 which were respectively downregulated and upregulated following arsenic induction were more efficiently restored to their near normal levels by T11TS alone in comparison with the combined regimen. Similar results were obtained with the apoptotic proteins studied, FasL, BAX, BCL2 and the caspases 3, 8 and 9, where again T11TS proved more potent than in combination with MiADMSA in preventing lymphocyte death. The results thus indicate that T11TS alone is more efficient in immune re-establishment after arsenic exposureas compared to combination therapy with T11TS+MiADMSA.

• ALGAE
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• v.30 no.2
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• pp.147-161
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• 2015

Brown algal extracts have long been used as feed supplements to promote health of farm animals. Here, we show new molecular insights in to the mechanism of action of a fucose containing polymer (FCP) rich fraction from the brown seaweed Ascophyllum nodosum using the Caenorhabditis elegans-Pseudomonas aeruginosa PA14 infection model. FCP enhanced survival of C. elegans against pathogen stress, correlated with up-regulation of key immune response genes such as: lipases, lysozyme (lys-1), saponin-like protein (spp-1), thaumatin-like protein (tlp-1), matridin SK domain protein (msk-1), antibacterial protein (abf-1), and lectin family protein (lfp). Further, FCP caused down regulation of P. aeruginosa quorum sensing genes: (lasI, lasR, rhlI, and rhlR), secreted virulence factors (lipase, proteases, and elastases) and toxic metabolites (pyocyanin, hydrogen cyanide, and siderophore). Biofilm formation and motility of pathogenic bacteria were also greatly attenuated when the culture media were treated with FCP. Interestingly, FCP failed to mitigate the pathogen stress in skn-1, daf-2, and pmk-1 mutants of C. elegans. This indicated that, FCP treatment acted on the regulation of fundamental innate immune pathways, which are conserved across the majority of organisms including humans. This study suggests the possible use of FCP, a seaweed component, as a functional food source for healthy living.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.13
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• pp.5359-5364
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• 2015

Background: Multiple complex pathways are operable in the evolution of cutaneous T cell lymphomas (CTCLs). These pathways involve interaction between neoplastic T cells and cells of the immune system (especially dendritic cells and the non-malignant T cells). Granulysin is a proinflammatory antimicrobial peptide which has an immune alarmin function, activating dendritic cells, as well as an active role in tumor immunology and prognosis. FOXP3+ regulatory T cells Tregs are an important player in the immune system. Much controversy is found in the literature about the role of Tregs in CTCL. Aim: The present study aimed to investigate the expression of granulysin and FOXP3 in mycosis fungoides (MF), its precursor lesion large plaque parapsoriasis and its leukemic form ;$s\acute{e}ezary$ syndrome (SS). Materials and Methods: Immunohistochemical expression of granulysin and FOXP3 were assessed in lesional skin biopsies taken from 58 patients (4 large plaque parapsoriasis, 48 MF and 6 SS). Results: Granulysin positivity was cytoplasmic and higher in MF than in parapsoriasis en plaque and higher in the more advanced stages of MF (p<0.001). All groups showed significant differences between each other except between MF tumor stage and SS. FOXP3 positivity was nuclear and higher in early stage MF (plaque and patch stages) than in tumor stages and SS (p<0.001). However the FOXP3 count was lower in parapsoriasis en plaque than in other stages of MF. All the groups showed significant differences between each other except between parapsoriasis and SS and between patch and plaque stages of MF. Conclusions: The present study supports a role for granulysin in MF progression and proposes a novel hypothesis about the effect of FOXP3 +veTregs in the suppression of the activity of the neoplastic cells in MF.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.2
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• pp.414-424
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• 2007

Adenophorae Radix (AR), Liriopis Tuber (LT), Dendrobii Monile (DM), Polygonati Officinalis (PO), Polygonati Rhizoma (PR) have been used to treated a variety condition/diseases in traditional oriental medicine. The present study was conducted to investigate the immunmodulatory effects of the water-extracted AR, LT, DH, PO and PR. In spleen cell proliferation assay, DH was significantly enhanced mitogenic activity compared with control group. In RT-PCR, DH ad PO induced IL-2 and IFNr cytokine gene expression in mouse spleen cells. Methotrexate(MTX), immune supression agent, was significantly inhibited mouse spleen cell proliferation(1600 mg/ml). In spite of MTX treatement, DH and PO sustained the spleen cell proliferation, In the flow cytometry analysis, DH stimulated mouse spleen cells showed an increase in B-cell phenotype (CD45R/B220). The water-extracted DH and PO inhibited NO production and iNOS expression in LPS-stimulated RAW 264.7 macrophage cell. DH induced IL-2 and IFNg gene expression in human peripheral mononuclear cells. The GC-MS analysis show that the main component of water-extracted DH was b-Nitroethyl alcohol. The main components of water-extracted PO were Dipirartril-tropico, Methyl sulfoxide and Demsodrox. These data suggest that among these extracts, DH has a protective effcet of immune suppression caused by MTX. DH may be enhance cellular and humoral immune response by the regulation of cytokine gene expression, NO production and B cell production.