• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2005년도 BIOINFO 2005
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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.

• Environmental Analysis Health and Toxicology
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• 제17권4호
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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.

• Parasites, Hosts and Diseases
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• 제48권1호
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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.

• Parasites, Hosts and Diseases
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• 제55권6호
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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.

• Journal of Acupuncture Research
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• 제34권2호
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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.

• 생명과학회지
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• 제22권3호
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• pp.298-305
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• 2012

Lutein은 식물에서 발견되는 carotenoid 계열에 속하는 물질로 항산화 기능을 가지고 있는 것으로 널리 알려져 있지만, 호흡기 질환과 관련하여 아직까지 lutein의 효능과 작용 기작이 잘 알려져 있지 않다. Ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델에서 lutein은 기도 과민성을 억제하였고, 기관지 폐포 세척액에서 OVA의 감작에 의하여 증가한 각종 염증성 지표들을 감소시켰다. 또한, OVA의 감작에 의하여 증가한 제2형 협조 T 세포(Th2 cell)의 증가된 반응을 약화시키는 결과를 볼 수 있었다. 본 실험에서 lutein이 ovalbumin (OVA)으로 유도한 천식 생쥐 모델에서 제 2형 협조 T세포의 싸이토카인과 유전자 발현을 조절할 수 있는 면역약리학적 기능을 할 수 있는 물질로서의 가능성이 있음을 확인할 수 있었다.

• 대한수의학회지
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• 제41권2호
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• pp.211-218
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• 2001

병원성 내장리슈만편모충(Leishmania donovani)에서 추출한 GP63 또는 LPG 항원을 liposome으로 캡슐화하고 보강제로서 BCG를 조합하여 DBA-2N 마우스에 면역접종을 한 후, 내장리슈만편모충의 병원성 amastigote를 접종하여 이들 물질의 방어면역 효과를 관찰하였다. 그 결과 GP63 과 LPG, 그리고 BCG를 모두 첨가하여 접종한 마우스의 간 조직에서 유의성 있는 내장리슈만편모충의 감소가 관찰되었으나 감소율은 27.4%에 불과하였다. 실험적 피부리슈만편모충증에 대하여 성공적인 방어면역성을 나타낸 GP63이 내장리슈만편모충 감염에 대하여 방어면역성을 상실한 원인을 분석하기 위한 실험에서 C3H 마우스에 GP63-GST 단백질과 BCG를 혼합하여 면역접종하고 내장리슈만편모충의 병원성 amastigote로 접종한 후, 혈청 내 특이항체와 비장세포에서의 감마인터페론 및 IL-5의 생산을 관찰하였다. 그 결과 GP63-GST와 BCG를 혼합하여 면역 접종한 마우스의 간 조직에서도 유의성 있는 amastigote의 감소는 관찰되지 않았다. 한편 이들 마우스의 비장세포에서는 BCG 만을 접종한 군에 비해 10배 이상의 감마인터페론과 3배의 IL-5가 생산되었다. 이와 같은 사실은 GP63-GST 단백질과 BCG를 혼합하여 접종한 마우스에서 Th1 및 Th2 타입 면역반응이 모두 활성화되었음을 시사하며, Th1 뿐만 아니라 Th2 타입 면역 반응도 함께 활성화된 것이 실험적 내장리슈만편모충 감염에 대한 방어면역에 실패한 원인 중의 하나일 것으로 사료되었다.

• Journal of Veterinary Science
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• 제19권6호
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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.

• 한국식품영양과학회지
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• 제35권10호
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• pp.1329-1335
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• 2006

AIDS로의 진행과정은 단순히 몇몇 기작에 의한 것이 아니라 여러 경로를 거쳐 발생하며 그 진행속도도 개개인에 따라 다양하게 나타나고 있다. 본 연구에서는 쥐 AIDS 모델을 이용하여 항산화호르몬으로 알려진 DHEAS의 면역조절 효과를 확인하고자 하였다. DHEAS의 투여는 LP-BM5 retrovirus 감염으로 인한 T와 B 임파구의 mitogenesis를 증가시켰으며 Th1/Th2 type cytokines의 발현에도 영향을 미쳤는데 주로 전사수준에서 작용한 것으로 생각된다/ 또한 retrovirus 감염으로 인한 간조직의 지질과산화 유발을 억제하여 조직 내의 항산화제인 vitamin E의 함량을 유지시킴으로 NF-kB의 활성화를 통한 retrovirus의 복제를 억제시켜 Th1/Th2 type cytokines의 불균형적인 발현을 저해하였을 것으로 여겨진다. 따라서 쥐 AIDS모델에 있어서 DHEAS의 면역조절 효과를 확인한 본 연구는 향후 HIV감염 이후 AIDS로의 진행 과정 시 항산화제의 역할과 기작 규명에 대한 가능성을 제시할 수 있을 것으로 생각된다.

• Biomolecules & Therapeutics
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• 제17권4호
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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.