• Tuberculosis and Respiratory Diseases
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• 제45권1호
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• pp.90-98
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• 1998

연구배경: 외인성 천식은 TH2세포에 의한 매개체의 주요 원인중 하나임이 밝혀지고 있다. 연구자 등은 증상 악화로 내원한 기관지천식 환자와 만성기관지염 환자 사이에 T 림프구 아형의 변화와 싸어토카인 (cytokine)들의 변화에 차이가 있는지 연구하고자 하였다. 방 법: 기관지 천식으로 치료중인 환자 중에서 천식 악화로 내원한 외인성 천식 15예와 만성기관지염 환자 12예, 그리고 정상인 5예를 대상으로 하였다. 환자의 병력과 임상소견, 피부반응검사, 그리고 특이 IgE 측정을 시행하고 단일항체인 CD62L를 이용하여 flow cytometer로 림프구아형을 분석하고 ELISA kit(Quantikine IL-4, IFN-$\gamma$)를 이용하여 IL-4, IFN-$\gamma$을 측정하였다. 결 과: CD4+ T 림프구는 기관지천식환자에서 $40{\pm}7.2%$ 만성기관지염 환자 $43{\pm}19.8%$, 정상인에서 $41{\pm}14%$로 기관지 천식환자와 다른 군간에 의미있는 차이는 없었다(p=0.49, p=0.75). CD62L(L-selectin) 양성 T 림프구의 세포 백분율은 기관지천식환자(n=7) 에서 $24.8{\pm}23.6%$였고, 만성기관지염환자(n=5) $17.0{\pm}16.9%$, 정상인(n=5) $16.7{\pm}16.4%$으로 기관지천식환자와 다른 군간에 의미있는 차이는 없었다(p=0.32, p=0.22). 혈청 IL-4 의 활성도는 기관지천식환자에서 $3.6{\pm}0.9pg/ml$ 만성기관지염 환자 $2.0{\pm}1.2pg/ml$, 정상인에서 $0.7{\pm}1.1pg/ml$로 기관지 천식환자에서 만성기관지염 환자군에 비하여 증가되어 있었으며 (p=0.02) 정상인보다 증가되어 있었다(p=0.006)(Fig. 4). 혈청 INF-$\gamma$의 활성도는 증가되지 않았다. 결 론: 결론적으로 CD62L 양성 T 림프구의 세포 백분율은 기관지천식환자에서 증가되어 있지 않았으며 혈청 IL-4의 활성도는 기관지천식환자에서 증가되어 있었다.

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.492-497
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• 2021

Levels of sphingosine 1-phosphate (S1P), an intercellular signaling molecule, reportedly increase in the bronchoalveolar lavage fluids of patients with asthma. Although the type 4 S1P receptor, S1P₄ has been detected in mast cells, its functions have been poorly investigated in an allergic asthma model in vivo. S1P₄ functions were evaluated following treatment of CYM50358, a selective antagonist of S1P₄, in an ovalbumin-induced allergic asthma model, and antigen-induced degranulation of mast cells. CYM50358 inhibited antigen-induced degranulation in RBL-2H3 mast cells. Eosinophil accumulation and an increase of Th2 cytokine levels were measured in the bronchoalveolar lavage fluid and via the inflammation of the lungs in ovalbumin-induced allergic asthma mice. CYM50358 administration before ovalbumin sensitization and before the antigen challenge strongly inhibited the increase of eosinophils and lymphocytes in the bronchoalveolar lavage fluid. CYM50358 administration inhibited the increase of IL-4 cytokines and serum IgE levels. Histological studies revealed that CYM50358 reduced inflammatory scores and PAS (periodic acid-Schiff)-stained cells in the lungs. The pro-allergic functions of S1P₄ were elucidated using in vitro mast cells and in vivo ovalbumin-induced allergic asthma model experiments. These results suggest that S1P₄ antagonist CYM50358 may have therapeutic potential in the treatment of allergic asthma.

• 대한약침학회지
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• 제5권1호
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• pp.135-151
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• 2002

Objective: This study was eanied out to investigate the effects of Raphani Semen on immuno-response in the mouse model of allergic asthma. Methods: In this study, BALB/C mice were divided into 6 groups: Normal (Non-treated group), Control (Group with not treated after allergic sensitization and induction by ovalbumin), Treat I (Group with the oral administration of saline after allergic sensitization and induction by ovalbumin), Treat n (Allergic asthma group treated with acupuncture (BL 13)), Treat III (Allergic asthma group treated with the oral administration of Raphani Semen) and Treat lV (Allergic asthma group treated with the herbal-acupuncture of Raphani Semen (BL 13)). The effect on cytokine was assessed by measuring cytokine (lL-2, IL-4, IL-5, IL-10, IL-12, IFN-r) in bronchoalveoar lavage fluid(ELISA). ResuJts : The results obtained as follows: 1. The production of Interleukin-2 was decreased significantly in Treat I group, Treat n group and Treat IV group as compared with Control group. 2. The production of Interleukin-4 was decreased significantly in Treat I group, Treat II group and Treat IV group as compared with Control group. Among them. the production of Interleukin-4 was decreased remarkably in Treat IV group as compared with other groups. 3. The production of Interleukin-5 was decreased significantly in Treat I group and Treat IV group as compared with Control group. 4. The production of Interleukin-10 was decreased significantly in Treat I group and Treat III group as compared with Control group. 5. The production of Interleukin-12 was all decreased significantly in Treat I group, Treat n group, Treat m group and Treat IV group as compared with Control group. 6. The production of Intelferon- showed no significant changes in Treat I group, Treat n group. Treat m group and Treat Ⅳ group as compared with Control group. Conclusion: These results show that the production of Interleukin-4, 5 was decreased significantly in aJlergic asthma group treated with the herbal-acupuncture of Raph Semen (BL 13), It is known that inactivity of Th2 cell constrained the revelation and controlled hypersenstive action. As to this mechanism, it is suggested that the herbal-acupuncture of Raphani Semen(BL 13) constrained the revelation of allergic asthma.

• 한방안이비인후피부과학회지
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• 제29권2호
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• pp.65-81
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• 2016

Objectives : Haedoksamul-tang (HSTE), a water extract from a mixture of Phellodendri Cortex, Coptidis, Scutellariae Radix, Gardeniae Fructus, Angelica acutiloba Radix, Cnidii Rhizoma, Paeoniae Radix, Rehmanniae Radix, has been traditionally used for allergic skin diseases such as atopic dermatitis and contact dermatitis in oriental countries. However, little is known about the effects of aqueous extract of HSTE on trimellitic anhydride (TMA)-induced contact hypersensitivity (CHS) in a mouse model. Methods : In this study, we investigate the pharmacological effects of HSTE on TMA-induced CHS in Balb/c mice. Contact hypersensitivity was induced in mice by topically sensitizing and challenging with TMA in flank skin and ears during oral administration (for 17 days) and topical treatment (30 min before challenge) with HSTE. We examined the effects of HSTE on IgE and IgG1 levels, inflammatory parameters in ear tissues, CD4⁺/CD8⁺ ratio, cytokine and chemokine production in sera, tissues, and immune cells from TMA-sensitized mice.Results : Oral and topical administration with HSTE reduced, in a dose dependent manner, thickness and leukocyte infiltration of ear tissues and IgE levels in serum from mice sensitized with TMA. In addition, auricula lymph node cells isolated from TMA-sensitized mice significantly elevated the expression ratio of CD4⁺/CD8⁺ as well as increased the production of IL-4, IL-5, IL-13 and IFN-γ by ex vivo stimulation with antibodies against CD3 and CD28, and these inflammatory indexes, except for IFN-γ, were significantly suppressed by orally and topically administration of HSTE. Furthermore, stimulation of auricula lymph node cells from TMA-sensitized mice with antibodies against CD3 and CD28 increased the production of MCP-1/CCL2 and MIP-1α/CCL3, and these effects were inhibited in a dose-dependent manner in cells from mice treated with HSTE. Conclusions : These results suggest that HSTE can be used for treating contact hypersensitivity by inhibiting leukocyte infiltration as well as production of serum IgE and chemokine/Th2 cytokine in an animal model.

• IMMUNE NETWORK
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• 제13권4호
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• pp.157-162
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• 2013

Application of vaccine materials through oral mucosal route confers great economical advantage in animal farming industry due to much less vaccination cost compared with that of injection-based vaccination. In particular, oral administration of recombinant protein antigen against foot-and- mouth disease virus (FMDV) is an ideal strategy because it is safe from FMDV transmission during vaccine production and can induce antigen-specific immune response in mucosal compartments, where FMDV infection has been initiated, which is hardly achievable through parenteral immunization. Given that effective delivery of vaccine materials into immune inductive sites is prerequisite for effective oral mucosal vaccination, M cell-targeting strategy is crucial in successful vaccination since M cells are main gateway for luminal antigen influx into mucosal lymphoid tissue. Here, we applied previously identified M cell-targeting ligand Co1 to VP1 of FMDV in order to test the possible oral mucosal vaccination against FMDV infection. M cell-targeting ligand Co1-conjugated VP1 interacted efficiently with M cells of Peyer's patch. In addition, oral administration of ligand-conjugated VP1 enhanced the induction of VP1-specific IgG and IgA responses in systemic and mucosal compartments, respectively, in comparison with those from oral administration of VP1 alone. In addition, the enhanced VP1-specific immune response was found to be due to antigen-specific Th2-type cytokine production. Collectively, it is suggested that the M cell-targeting strategy could be applied to develop efficient oral mucosal vaccine against FMDV infection.

• IMMUNE NETWORK
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• 제11권4호
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• pp.203-209
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• 2011

Background: T cell immunoglobulin mucin containing molecule (TIM)-3 is expressed in differentiated Th1 cells and is involved in the suppression of the cytokine production by these cells. However, the regulation of the expression of other T cell genes by TIM-3 is unclear. Herein, we attempted to identify differentially expressed genes in cells abundantly expressing TIM-3 compared to cells with low expression of TIM-3. Methods: TIM-3 overexpressing cell clones were established by transfection of Jurkat T cells with TIM-3 expression vector. For screening of differentially expressed genes, gene fishing technology based on reverse transcription-polymerase chain reaction (RT-PCR) using an annealing control primer system was used. The selected candidate genes were validated by semi quantitative and real-time RT-PCR. Results: The transcription of TIMP-1, IFITM1, PAR3 and CCL1 was different between TIM-3 overexpressing cells and control cells. However, only CCL1 transcription was significantly different in cells transiently transfected with TIM3 expression vector compared with control cells. CCL1 transcription was increased in primary human $CD4^+$ T cells abundantly expressing TIM-3 but not in cells with low expression of TIM-3. Conclusion: CCL1 was identified as a differentially transcribed gene in TIM-3-expressing $CD4^+$ T cells.

• Journal of Microbiology and Biotechnology
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• 제33권4호
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• pp.441-448
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• 2023

Brucellosis is a contagious zoonotic disease that infects millions of people annually with hundreds of millions more being exposed. It is caused by Brucella, a highly infectious bacterial species capable of infecting humans with an estimated dose of 10-100 organisms. Sirtuin 1 (SIRT1) has been reported to contribute to prevention of viral diseases as well as a chronic infection caused by Mycobacterium bovis. Here, we investigated the role of SIRT1 in the establishment of Brucella abortus infection in both in vitro and in vivo systems using the reported SIRT1 activators resveratrol (RES), piceatannol (PIC), and ginsenoside Rg3 (Rg3). In RAW264.7 cells, SIRT1 activators did not alter the adherence of Brucella or Salmonella Typhimurium. However, reduced uptake of Brucella was observed in cells treated with PIC and Rg3, and survival of Brucella within the cells was only observed to decrease in cells that were treated with Rg3, while PIC treatment reduced the intracellular survival of Salmonella. SIRT1 treatment in mice via oral route resulted in augmented Brucella resistance for PIC and Rg3, but not RES. PIC treatment favors Th2 immune response despite reduced serum pro-inflammatory cytokine production, while Rg3-treated mice displayed high IL-12 and IFN-γ serum production. Overall, our findings encourage further investigation into the complete mechanisms of action of the different SIRT1 activators used as well as their potential benefit as an effective alternative approach against intracellular and extracellular pathogens.

• 한국식품과학회지
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• 제40권5호
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• pp.574-579
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• 2008

본 연구는 프로폴리스 추출물 및 발효 프로폴리스 추출물의 투여에 의한 면역활성에 미치는 영향을 검토하기 위하여 수행하였다. 프로폴리스 추출물 및 발효 프로폴리스 추출물을 체중 kg 당 50, 100, 200 mg/kg의 농도로 BALB/c 마우스에게 14일 동안 연속적으로 경구투여한 후, 이러한 시험물질 투여에 기인한 비장림프구와 창자간막 림프구의 증식능, 림프구의 아집단 비율의 변화 및 사이토카인 분비능을 측정하였다. 또한 비장 림프구로부터 NK 세포를 분리하여 YAC-1 세포를 살해하는 NK 세포의 활성을 측정하였다. 그 결과 프로폴리스 및 발효 프로폴리스의 투여에 의해 비장 림프구와 창자간막 림프구의 T 림프구($CD3^+$) 비율이 증가하는 경향을 보였으며, 이는 $CD4^+$와 $CD8^+$ T 림프구 비율의 증가에 기인하였다. 비장 및 창자간막 림프절로부터 분리한 림프구의 증식능도 프로폴리스 및 발효 프로폴리스 투여에 의해 증가되는 것을 관찰할 수 있었다. Th-1/Th-2 사인토카인 분비에 미치는 영향을 관찰한 결과 비장림프구에서는 발효 프로폴리스 추출물이 프로폴리스 추출물에 비하여 IFN-$\gamma$, IL-2, IL-4의 분비를 증강시키는 것을 확인할 수 있었다. 창자간막 림프구의 Th-2 사이토카인 분비증강은 고농도(200 mg/kg)의 프로폴리스 및 발효 프로폴리스 추출물 투여군에서만 관찰되었다. 프로폴리스 및 발효 프로폴리스 투여에 의해 YAC-1 세포를 살해하는 NK 세포의 활성도 유의적으로 증가하였다. 이상의 결과로, 프로폴리스 및 발효 프로폴리스 추출물의 경구투여는 체내 면역기능을 증강 시킬 수 있는 면역조절제로서의 가능성을 가지는 것으로 사료된다.

• 한국식품영양학회지
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• 제31권2호
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• pp.236-241
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• 2018

Flammulina velutipes is an edible mushroom and contains a lot of fiber, vitamin $B_1$, $B_2$, niacin and folic acid. This study was conducted to explore the effects of the Flammulina velutipes mushroom on immune cells and immunity. Th1 cytokine productions as $IFN-{\gamma}$, $TNF-{\alpha}$, and IL-2 were measured in an activated macrophage by Flammulina velutipes water extract in seven concentrations (0, 5, 10, 50, 100, 250, 500, and $1,000{\mu}g/mL$). Also, the splenocyte proliferation index was measured at 48 hours after treatment of the Flammulina velutipes water extract in seven concentrations or mitogen, LPS and ConA. The $IFN-{\gamma}$ and $TNF-{\alpha}$ productions were increased by treatment of the Flammulina velutipes water extract. The $TNF-{\alpha}$ production was significantly higher in the $50{\sim}1,000{\mu}g/mL$ Flammulina velutipes water extract treated macrophages. The $IFN-{\gamma}$ production of macrophages treated with the Flammulina velutipes water extract increased significantly in all groups, and the highest $1000{\mu}g/mL$ concentration. The splenocyte proliferation index was enhanced when the $10{\sim}1,000{\mu}g/mL$ Flammulina velutipes water extracts were treated compared to the control. These primary results suggest that Flammulina velutipes may enhance the immune function by activation of the macrophage and spleen cell.

• 약학회지
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• 제46권4호
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• pp.258-264
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• 2002

Zinc plays an important role in immunobiological responses, while excessive zinc attenuates immune functions in a dose-dependent manner. Zinc excess has been reported to increase levels of plasma prostaglandin E$_2$ (PGE$_2$), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inflammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE$_2$ synthesis, on the proinflammatory cytokine and lymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered i.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$ levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1$\beta$. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-${\gamma}$ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-${\gamma}$ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-1$\beta$ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN-${\gamma}$ but not IL-2.