• Proceedings of the Korean Society for Bioinformatics Conference
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• 2005.09a
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• pp.344-347
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• 2005

Helper T(Th) cells regulate immune response by producing various kinds of cytokines in response to antigen stimulation. The regulatory functions of Th cells are promoted by their differentiation into two distinct subsets, Th1 and Th2 cells. Th1 cells are involved in inducing cellular immune response by activating cytotoxic T cells. Th2 cells trigger B cells to produce antibodies, protective proteins used by the immune system to identify and neutralize foreign substances. Because cellular and humoral immune responses have quite different roles in protecting the host from foreign substances, Th cell differentiation is a crucial event in the immune response. The destiny of a naive Th cell is mainly controlled by cytokines such as IL-4, IL-12, and IFN-${\gamma}$. To understand the mechanism of Th cell differentiation, many mathematical models have been proposed. One of the most difficult problems in mathematical modeling is to find appropriate kinetic parameters needed to complete a model. However, it is relatively easy to get qualitative or linguistic knowledge of a model dynamics. To incorporate such knowledge into a model, we propose a novel approach, fuzzy continuous Petri nets extending traditional continuous Petri net by adding new types of places and transitions called fuzzy places and fuzzy transitions. This extension makes it possible to perform fuzzy inference with fuzzy places and fuzzy transitions acting as kinetic parameters and fuzzy inference systems between input and output places, respectively.

• Parasites, Hosts and Diseases
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• v.55 no.6
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• pp.587-599
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• 2017

The immune response against Trichinella spiralis at the intestinal level depends on the $CD4^+$ T cells, which can both suppress or promote the inflammatory response through the synthesis of diverse cytokines. During the intestinal phase, the immune response is mixed (Th1/Th2) with the initial predominance of the Th1 response and the subsequent domination of Th2 response, which favor the development of intestinal pathology. In this context, the glucocorticoids (GC) are the pharmacotherapy for the intestinal inflammatory response in trichinellosis. However, its therapeutic use is limited, since studies have shown that treatment with GC suppresses the host immune system, favoring T. spiralis infection. In the search for novel pharmacological strategies that inhibit the Th1 immune response (proinflammatory) and assist the host against T. spiralis infection, recent studies showed that resiniferatoxin (RTX) had anti-inflammatory activity, which decreased the serum levels of IL-12, $INF-{\gamma}$, $IL-1{\beta}$, $TNF-{\alpha}$, NO, and $PGE_2$, as well the number of eosinophils in the blood, associated with decreased intestinal pathology and muscle parasite burden. These researches demonstrate that RTX is capable to inhibit the production of Th1 cytokines, contributing to the defense against T. spiralis infection, which places it as a new potential drug modulator of the immune response.

• Parasites, Hosts and Diseases
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• v.48 no.1
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• pp.23-33
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• 2010

An understanding of the nature of the immune response to asexual erythrocytic stages of malaria parasites will facilitate vaccine development by identifying which responses the vaccine should preferentially induce. The present study examined and compared the immune responses of NIH mice in either single or mixed infections with avirulent (DK) or virulent (DS) strains of Plasmodium chabaudi adami using the ELISA test for detecting and measurement of cytokines and antibody production. In both single and mixed infections, the study showed that both cell- and antibody-mediated responses were activated. In all experiments, an early relatively high level of IFN-$\gamma$ and IgG2a during the acute phase of the infection, and later elevation of IL-4 and IgG1, suggested that there was a sequential Th1/Th2 response. However, in the avirulent DK strain infection a stronger Th1 response was observed compared to the virulent DS strain-infection or in mixed infections. In the virulent DS infection, there was a stronger Th2 response compared to that in the DK and mixed infections. The faster proliferation rate of the virulent DS strain compared to the DK strain was also evident.

• Environmental Analysis Health and Toxicology
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• v.17 no.4
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• pp.325-332
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• 2002

A helper T(Th)1-mediated response is known to enhance cell -mediated immunity, while a Th2-mediated response is associated with the humoral immunity that if elevated IgE levels and eosinophilia. Prostaglandin (PG)E$_2$results in the decreased capability of Iymphocytes to produce Thl cytokines, with a shift toward a Th2 cytokine response. Chlorpyrifos (CPF) has been reported to impair the blastogenesis and response of T Iymphocytes. CPF also induces delayed febrile effects, which results from the activation of COX -PGE$_2$pathway. The purpose of this study is to determine the effort of CPF on the in vitro production of Th cytokines and the role of PGE$_2$on the CPF-induced production of Th cytokines. Splenocytes obtained from male BALB/c mice were pretreated with CPF(0.1, 1, 10 and 100$\mu$M) in the presence of absence of indomethacin or PGE$_2$for 12 h and then were incubated with concanavalin (Con) A for 48 h. These results showed that CPF remarkedly reduced the production of splenic interleukin (IL)-2 and interferon (IFN)-γ in a dose-dependent manner. CPF significantly increased the splenic IL-4 production at low doses (0.1 and 1$\mu$M) but did not affect at high doses (10 and 100 $\mu$M). Indomethacin reduced the CPF-decreased production of IL-2 and IFN-γ in a dose -dependent manner and significantly attenuated the production of IL-4 increased by CPF 0.1 $\mu$M. High dose of CPF significantly reduced the PGE$_2$-decreased production of IL-2 and IFN-γ, while the PGE$_2$- induced production of IL-4 was significantly enhanced by CPF 1 $\mu$M. These findings suggest that CPF nay down-regulate the immune response of Th 1 type by the suppressed production of IL-2 and IFN-γ, with a shift toward a Th2 cytokine response. The CPF-decreased production of Thl cytokines may not be mediated by endogenous PGE$_2$. Also, CPF may attenuate the exogenous PGE$_2$-decreased Th 1 immune response in a dose--dependent manner but may affect dose-independently the PGE$_2$-induced Th2 immune response.

• Journal of Acupuncture Research
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• v.34 no.2
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• pp.39-48
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• 2017

Objectives : In this study, we investigated the immunomodulatory and antioxidant effect of MOK, a pharmacopuncture medicine, in concanavalin A (Con A)-stimulated mouse splenocytes. Methods : Primary splenocytes were isolated from ICR mice. The splenocytes were treated with MOK extract (1.25, 2.5, 5, 10, and 20 mg/mL) for 30 min and then stimulated with Con A (200 ng/mL) for the indicated times. Cell viability of the splenocytes was measured using an MTT assay. The mRNA expression of Th1/Th2 cytokines ($IFN-{\gamma}$, IL-4, IL-10, and Foxp3) and antioxidant enzymes (HO-1 and MnSOD) was measured by RT-PCR. Results : Addition of MOK extract at 2.5, 5, and 10 mg/mL in Con A-stimulated splenocytes significantly decreased the production of $IFN-{\gamma}$ and significantly increased the expression of IL-4, IL-10, and Foxp3 mRNA. MOK extract also increased the mRNA expression of HO-1 and MnSOD in splenocytes. Conclusion : MOK extract modulated the Th1/Th2 immune response via the regulation of cytokine levels in splenocytes and exerted an antioxidant effect via the upregulation of antioxidant proteins.

• Journal of Veterinary Science
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• v.19 no.6
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• pp.817-826
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• 2018

The bursa of Fabricius (BF) is a central humoral immune organ unique to birds. Four bursal peptides (BP-I, BP-II, BP-III, and BP-IV) have been isolated and identified from the BF. In this study, the immunoadjuvant activities of BPs I to IV were examined in mice immunized with H9N2 avian influenza virus (AIV) vaccine. The results suggested that BP-I effectively enhanced cell-mediated immune responses, increased the secretion of Th1 (interferon gamma)- and Th2 (interleukin-4)-type cytokines, and induced an improved cytotoxic T-lymphocyte (CTL) response to the H9N2 virus. BP-II mainly elevated specific antibody production, especially neutralizing antibodies, and increased Th1- and Th2-type cytokine secretion. BP-III had no significant effect on antibody production or cell-mediated immune responses compared to those in the control group. A strong immune response at both the humoral and cellular levels was induced by BP-IV. Furthermore, a virus challenge experiment followed by H&E staining revealed that BP-I and BP-II promoted removal of the virus and conferred protection in mouse lungs. BP-IV significantly reduced viral titers and histopathological changes and contributed to protection against H9N2 AIV challenge in mouse lungs. This study further elucidated the immunoadjuvant activities of BPs I to IV, providing a novel insight into immunoadjuvants for use in vaccine design.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.14.1-14.26
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• 2024

The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4⁺ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8⁺ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8⁺ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4⁺ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

• Archives of Pharmacal Research
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• v.29 no.11
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• pp.1042-1048
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• 2006

Plasmid DNA vaccines encoding the hepatitis B virus (HBV) surface and hepatitis C virus (HCV) envelope antigens, respectively, were constructed, and attempt were made to find the possibility of a divalent vaccine against HBV and HCV. The expression of each plasmid in Cos-1 cells was confirmed using immunocytochemistry. To measure the induced immune response by these plasmids in vivo, female BALB/c mice were immunized intramuscularly with $100\;{\mu}g$ of either both or just one of the plasmids. Anti-HBV and HCV-specific antibodies and related cytokines were evaluated to investigate the generation of both humoral and cellular immune responses. As a result, specific anti-HBV and anti-HCV serum antibodies from mice immunized with these plasmids were observed using immunoblot. The levels of IL-2 and RANTES showing a $Th_{1}$ immune response were significantly increased, but there was no change in the level of IL-4 ($Th_{1}$ immune response) in any of the immunized groups. Compared with each plasmid DNA vaccine, the combined vaccine elicited similar immune responses in both humoral and cell-mediated immunities. These results suggest that the combined DNA vaccine can induce not only comparable immunity experimentally without antigenic interference, but also humoral and $Th_{1}$ dominant cellular immune responses. Therefore, they could serve as candidates for a simultaneous bivalent vaccine against HBV and HCV infections.

• Archives of Pharmacal Research
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• v.25 no.6
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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.

• Journal of Life Science
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• v.22 no.3
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• pp.298-305
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• 2012

The general term flavonoids is often used to categorize a family of natural compounds that are highly abundant in all higher plants, and which in recent years have attracted scientific interest as therapeutics. Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. It is found in green vegetables such as spinach and kale, and has been demonstrated to exert anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. In this study, we attempt to determine whether lutein regulates inflammatory mediators in an ovalbumin (OVA)-induced murine asthma model. To address this, mice were sensitized and challenged with OVA, and then treated with lutein before the last OVA challenge. Administration of lutein significantly suppressed the OVA-induced airway hyper-responsiveness. It also resulted in a significant alleviation of the infiltration of inflammatory cells into the bronchoalveolar lavage. Additionally, lutein attenuated the increased expression of Th2 responses in OVA-challenged mice. These results demonstrate that lutein is a potent inhibitor that reduces Th2 immune responses. Furthermore, they show that the immunopharmacological function is mediated by a pathway that involves and is regulated by Th2 immune response.