• Journal of Microbiology and Biotechnology
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• 제26권3호
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• pp.469-476
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• 2016

This study was undertaken to evaluate the immunomodulatory effect of dead nano-sized Lactobacillus plantarum (nLp) in RAW 264.7 cells and murine primary splenocytes. nLp is a dead, shrunken, processed form of L. plantarum nF1 isolated from kimchi (a traditional Korean fermented cabbage) and is less than 1 μm in size. It was found that nLp treatment stimulated nitric oxide (NO) production more in RAW 264.7 macrophages than pure live L. plantarum (pLp), and that the stimulatory properties were probably largely derived from its cell wall. In addition, nLp induced murine splenocyte proliferation more so than pLp; in particular, a high dose of nLp (1.0 × 10¹¹ CFU/ml) stimulated proliferation as much as lipopolysaccharide at 2 μg/ml. Moreover, according to our cytokine profile results in splenocytes, nLp treatment promoted Th1 (TNF-α, IL-12 p70) responses rather than Th2 (IL-4, IL-5) responses and also increased Th17 (IL-6, IL-17A) responses. Thus, nLp stimulated NO release in RAW 264.7 cells and induced splenocyte proliferation more so than pLp and stimulated Th1 and Th17 cytokine production. These findings suggested that dead nLp has potential use as a functional food ingredient to improve the immune response, and especially as a means of inducing Th1/Th17 immune responses.

• 생명과학회지
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• 제20권4호
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• pp.503-510
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• 2010

대부분의 알려진 알러젠들은 단백분해효소의 성격을 가지고 있고 이는 알레르기 반응에서 Th2 면역 반응을 일으키는 데 중요한 역할을 하는 것으로 알려져 있다. 이러한 단백분해효소들과 반응하는 것으로 알려진 protease activated receptor (PAR) 는 4가지 종류가 있으며, 이 중 PAR2의 경우 알레르기 질환과 많은 상관관계를 보여 많은 연구가 되고 있다. 본 연구는 Aspergillus protease 알러젠에 의한 초기 및 만성 Th2 면역반응에서 PAR2 의 역할을 규명하기 위해 Aspergillus protease 알러젠으로 정상쥐와 PAR2 유전자 결핍쥐 모두 Th2 반응을 유도한 후 면역세포의 침윤 정도 및 Th2 관련 cytokine 및 chemokine 유전자들의 발현 정도를 비교하였다. 그 결과 Aspergillus protease 알러젠으로 비강내로 1회 처리했을 경우 중성구의 침윤이 두드러지는데, 이때 PAR2 결핍 마우스는 이러한 면역세포의 침윤이 유의적으로 감소하였다. 또한, 이와 관련된 IL-25, TSLP, Eotaxin 유전자들의 발현 역시 PAR2 결핍 마우스에 현저히 감소하였다. 한편, Aspergillus protease 알러젠으로 비강내로 6회 처리했을 경우 중성구 대신 호산구의 침윤이 두드러지지만 PAR2 결핍 마우스에서 그 정도가 유의적으로 낮았다. OVA 특이 IgE와 IgG1 농도 역시 현저하게 PAR2 결핍 마우스에서 낮았고, CCL21의 발현이 PAR2 결핍마우스 MEF cells에서 현저히 감소하였다. Th2 초기 면역반응에서 가장 중요한 IL-25의 발현에 MAKP p38 pathway가 관여한다는 것을 이번 연구에서 알 수 있다. 본 연구를 통해 Aspergillus protease 알러젠으로 유도된 알러지성 기관지 염증 반응에서 초기 반응뿐만 아니라 만성반응에서도 PAR2가 중요한 것을 알 수 있다.

• Asian-Australasian Journal of Animal Sciences
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• 제23권1호
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• pp.106-115
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• 2010

Phosphorylated dextran (P-Dex) is an acidic polysaccharide that functions as an immune adjuvant. P-Dex is known to regulate immune response by maintaining a balance between Th1 and Th2 cells in vitro, and thus may also be important in the control of allergic reactions. In the current study, we report the optimum conditions required for the efficient phosphorylation of dextran without toxicity. We found that when dextran was heated at 160${^{\circ}C}$ for 24 h in phosphate buffer (pH 5.0), the resulting P-Dex demonstrated the highest phosphorus content (6.8%). We also report that P-Dex enhances mitogenic activity in mouse splenocytes and induces expression of CD69 and CD86 on the surface of B cells and dendritic cells (DC) in vitro. Oral administration of P-Dex to ovalubmin (OVA)-immunized mice was found to reduce antigen-induced cell proliferation and suppress the expression of CD86 on Th2-inducing DC via exogenous OVA stimulation. P-Dex was also found to increase IL-10 expression in the splenocytes of treated mice. These findings suggest that oral administration of P-Dex increases immunological tolerance and improves the specificity of immunological response to specific antigens.

• Archives of Pharmacal Research
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• 제23권5호
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• pp.531-534
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• 2000

Nitric oxide (NO), products of activated macrophages, have a great impact on the regulation of cytokine production. The role of NO in non-specific host cells is commonly accepted. On the contrary, its role as an immuno-regulatory molecule is still controversial. In this study, we have investigated the effect of NO on the production of cytokines from murine splenocytes and macrophages. S-nitroso-L-glutathione inhibited the release of both interferone-$\gamma$ and interleukin-2 produced by Th1 cells and tumor necrosis factor-$\alpha$ and interleukin-1$\beta$ produced by macrophages, but did not affect the release of interleukin-4 and interleukin-10 produced by Th2 cells. These results suggest that NO exerts a down-regulatory effect on the secretion of cytokines from Th1 cells and macrophages which are implicated in immune response. Thus, NO may have an important role as an immune-modulatory as well as effector molecule in the immune system.

• 동의생리병리학회지
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• 제19권1호
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• pp.262-269
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• 2005

Kamiinsamyangyoung-tang(KIT) has been widely used to treat amenorrhea and bradymenorrea caused from vital energy and blood deficit. KIT was composed of Insamyangyoung-tang, Cervi Cornu Pantotrichum and Hominis Placenta. The aim of this study is to investigate effect of KIT on Immune response and Blood formation. We investigated thymocytes, splenocytes population, ${\gamma}$-interferon, IL-2, IL-4, NO and phagocytic activity. We found that KIT had no effect on the Th and Tc cell population of thymocytes, Th cell population of splenocytes and ${\gamma}$-interferon quantity was decreased. KIT decreased the formation of Nitric Oxide from abdominal macrophage, on the other hand, it had no influence on the quantity of IL-2, IL-4.

• 한국약용작물학회지
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• 제26권1호
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• pp.72-81
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• 2018

Background: Polysaccharides are the most important functional constituent in Astragalus membranaceus. The purpose of the present study was to evaluate the effect of polysaccharides isolated from the aboveground parts of A. membranaceus (AMA) and polysaccharides isolated from the roots of A. membranaceus (AMR) immune function by modulated cytotoxic T cell and Th1- and Th2-related cytokines kinetics. Methods and Results: Sprague-Dawley rats were randomly divided into exhaustive exercise case groups and non-exercise case, AMA and AMR samples were administered orally for 30 days (500 mg/kg/day and 10 mg/kg/day, respectively) and were compared to those rats in the groups fed commercial sports drink (SPD) and vehicle. Both exhaustive exercise groups and non-exercise groups had a lower ratio of $CD4^+$ and $CD8^+$ cells in the spleens of the rat fed AMA and AMR compared to those in the rats fed SPD and vehicle group. These results suggested that AMA and AMR promote an increase in the proportion of cytotoxic T cells. The IL-4-producing T lymphocytes decreased significantly in the AMR (10 mg/kg/day) group compared to SPD and vehicle, whereas the AMA group increased the IL-4 concentration more than the SPD and vehicle in exhaustive exercise group. However, the populations of IFN-${\gamma}$-producing T lymphocytes of AMR and AMA increased. AMA decreased the concentration of IFN-${\gamma}$ to inhibit the Th1 response and thereby increased the concentration of IL-4 to induce a Th2 response that was related to humoral immunity in the non-exercise group. Conclusions: These results showed that, in addition to Th1/Th2 regulation, AMR and AMA played an important immuno-modulatory role after exhaustive exercise-induced Th1/Th2 lymphocyte imbalance, which might be correlated with cytokine producing immunoregulatory cells.

• Journal of Microbiology and Biotechnology
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• 제26권6호
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• pp.1132-1139
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• 2016

Brucellosis is a zoonotic disease caused by Brucella, a genus of gram-negative bacteria. Cytokines have key roles in the activation of innate and acquired immunities. Despite several research attempts to reveal the immune responses, the mechanism of Brucella infection remains unclear. Therefore, immune responses were analyzed in mice immunized with nine recombinant proteins. Cytokine production profiles were analyzed in the RAW 264.7 cells and naive splenocytes after stimulation with three recombinant proteins, metal-dependent hydrolase (r0628), bacterioferritin (rBfr), and thiamine transporter substrate-binding protein (rTbpA). Immune responses were analyzed by ELISA and ELISpot assay after immunization with proteins in mice. The production levels of NO, TNF-α, and IL-6 were time-dependently increased after having been stimulated with proteins in the RAW 264.7 cells. In naive splenocytes, the production of IFN-γ and IL-2 was increased after stimulation with the proteins. It was concluded that two recombinant proteins, r0628 and rTbpA, showed strong immunogenicity that was induced with Th1-related cytokines IFN-γ, IL-2, and TNF-α more than Th2-related cytokines IL-6, IL-4, and IL-5 in vitro. Conversely, a humoral immune response was activated by increasing the number of antigen-secreting cells specifically. Furthermore, these could be candidate diagnosis antigens for better understanding of brucellosis.

• Childhood Kidney Diseases
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• 제22권1호
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• pp.17-21
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• 2018

Thymic stromal lymphopoietin (TSLP) is an interleukin-7-like cytokine that is an important trigger and initiator of many allergic diseases. TSLP promotes a T-helper type 2 (Th2) cytokine response that can be pathological. A relationship is formed both at the induction phase of the Th2 response through polarization of dendritic cells to drive Th2 cell differentiation and at the effector phase of the response, by promoting the expansion of activated T cells and their secretion of Th2 cytokines and TSLP. In transgenic mice with TSLP overexpression, it has been reported that TSLP leads to the development of mixed cryoglobulinemic membranoproliferative glomerulonephritis. In addition, TSLP can play an important role in the pathogenesis of IgA nephropathy and systemic lupus erythematosus-related nephritis. From our knowledge of the role of TSLP in the kidney, further studies including the discovery of new therapies need to be considered based on the relationship between TSLP and glomerulonephritis.

• 한국축산식품학회지
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• 제31권3호
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• pp.420-427
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• 2011

The use of lactic-acid bacteria (LAB) is effective for preventing and curing immune disorders by activating the immune system in the digestive tract and the consequent immune response in the blood. In this study, LAB and mixed LABs were used in an atopic dermatitis (AD) mouse model. Alleviation of AD was observed based on the change in cytokine level and immunohistochemical staining. An ex vivo test showed that immunoglobulin-E and interleukin (IL)-4 levels were significantly lower in all groups treated with LAB than in the group treated with only 1-chloro-2,4-dinitrobenzene. Results of an in vivo test based on the ex vivo results showed that the scratch score decreased in all groups treated with the LAB and particularly decreased in the group treated with mixed LABs. Additionally, the T helper (Th) 1 cytokines interferon-gamma and IL-12p40 were upregulated by the LAB and mixed-LABs, whereas levels of the Th2 cytokine IL-4 were downregulated in a mouse model of AD-like skin lesions. Furthermore, hematoxylin & eosin and immunohistochemical staining of the dorsal area of the mice in each group showed that AD improved in the LAB-treated groups. These results suggest that LAB and mixed LABs inhibit the development of AD in NC/Nga mice by suppressing the Th2 cell response and increasing the Th1 cell response. Our results indicate that mixed LABs are better than LAB for treating AD-like skin lesions.

• Clinical and Experimental Pediatrics
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• 제53권12호
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• pp.985-988
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• 2010

The innate immune response is the first line of defense against microbial infections. Innate immunity is made up of the surface barrier, cellular immunity and humoral immunity. In newborn, immunologic function and demands are different to adults. Neonatal innate immunity specifically suppresses Th1-type immune responses, and not Th2-type immune responses, which are enhanced. And the impaired response of macrophages is associated with the defective innate immunity in newborn period. Toll-like receptors (TLRs) play a key roles in the detection of invading pathogens and in the induction of innate immune responses. In newborn, the expression of TLRs is age dependent, so preterm has low expression of TLRs. Also, there are defects in signaling pathways downstream of TLRs. As a consequence, the defects of TLRs activity cause the susceptibility to infection in the neonatal period.