• 대한본초학회지
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• 제24권1호
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• pp.79-88
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• 2009

Objectives : It has been recently shown that Piperis Longi Fructus (PLF) is involved in the reduction of eosinophil recruitment and production of Th2 cytokines in vivo. However, the main therapeutic mechanisms of PLF remains a matter of considerable debate. To investigate the therapeutic mechanisms of PLF, we examined the influence of PLF on regulatory T cells number, IgE, histamine production in vivo and Th1/Th2 cytokine balance in vitro. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by i.p. injections of 0.2 $m\ell$ alum-precipitated Ag containing 100 ${\mu}g$ of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 min/day on 3 days/week for 12 weeks(at a flow rate of 250 L/min, 2.5％ ovalbumin in normal saline) and PLF (150 mg/kg) were orally administered 3 times a week for 8 weeks. Splenocytes from C57BL/6 mice at 8 weeks of age were stimulated with anti-CD3 (1 mg/ml) plus anti-CD28 (1 mg/ml) antibody for 48hrs. IL-4 and IFN-$\gamma$ in the culture supernatants were measured by ELISA Results : The suppressive effects of PLF on asthma model were demonstrated by the increase the number of regulatory T cells and by reducing IgE, histamine production in vivo and modulation of Th1/Th2 cytokine balance. Conclusions : These results indicate that PLF has a deep inhibitory effects on asthma model mice by increase the number of regulatory T cells, and by reducing IgE, histamine production.

• 한국임상수의학회지
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• 제27권4호
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• pp.311-314
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• 2010

Bartonella henselae 는 고양이할큄병의 원인체이다. 고양이가 Bartonella spp.의 주된 보유숙주이기는 하지만, 최근 애완견의 할큄에 의한 고양이할큄병 발생이 보고되었다. 8두의 개에 1 ml의 인산완충식염수에 부유한 $2{\times}10^8CFU$의 B. henselae Houston-1을 0일에 피내주사하고, 동량을 21, 28, 36, 58, 64일째에 추가로 피내주사 하였다. B. henselae 감염을 nested PCR을 통해 확인하였다. B. henselae-PCR 양성군이 음성군에 비해 B. henselae로 말초혈액단 핵구를 자극한 후 얻은 배양상청액에서의 IFN-$\gamma$ 농도가 유의성 있게 높았다. B. henselae자극시, Th1활성을 보이는 개 말초혈액단핵구의 면역양상은 Th2활성을 보인다고 알려진 고양이와는 다른 것으로 보인다.

• 대한본초학회지
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• 제23권1호
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• pp.53-61
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• 2008

Objectives : The aim of this study was to investigative the effects of Gagambojungikgi-tang (GBT), a Korean herbal medicine, on the immune mediators, T cell proliferation and wound healing in the recombinant Sj26 (rSj26) antigen induced atopic dermatitis(AD) model mice. Methods : GBT is the water extracts prepared from mixture of Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Atractylodes Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Artemisia iwayomogi Herba, Scutellaria Radix, Lonicera japonica Flos. This is a modified prescription of Bojungikgi-tang, which has been used for the treatment of indigestion, and immunological disease in east-asian countries. GBT was orally administered or externally applied at difference doses. The levels of immune mediators [(IgE, IgG1, prostaglandin E2 (PGE2), Th1/Th2 cytokines], T cell proliferation, and wound healing in the rSj26 or chemical antigen induced AD model BALB/c were investigated. Results : GBT dose-dependently suppressed the release of TNF-${\alpha}$, IL-$1{\beta}$ (Th1 cytokines), IL-4, IL-10 (Th2 cytokines), PGE2 (inflammatory mediators) and T cell proliferation. But GBT increased the production of IFN-${\gamma}$ (Th1 cytokine). Furthermore, A wound healing effect of GBT was similar to external application of dexamethasone. Conclusions : These results suggest that GBT suppresses the inflammatory mediators and regulates the Thl/Th2 cytokines, and promotes the wound healing. Therefore, these properties may contribute to the strong anti-AD effect of GBT.

• 대한한방소아과학회지
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• 제21권1호
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• pp.87-116
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• 2007

Objectives : The purpose of this study is to examine of the effect of Kami-chungsimyeunjatang(KCSYJT) medicine on the atopy eruption control. Methods : The expression of IgE, IL-4, IL-6, $TNF-{\alpha}$, IgG2b, IgM, IgG2a and IgG1 level in serum, and $IFN-{\gamma}$ production by KCSYJT were analyzed. CD3e+/CD69+, CD4+/CD25+, B220+/IgE+ and B220+/CD23+ positive cells by flow cytometry in splenocytes were assayed and the revelation of CD3e+/CD69+, CD4+/CD8+ and CD4+/CD25+ marker in PBMC, spleen and DLN were observed. The outturn of IL-4, eotaxin 2, CCR3, TARC mRNA in splenocytes werw observed. We also analyzed NC/Nga mice's ear, DLN and neck-back skin after biopy and dye by H&E, and toluidine staining (mast cells marker) method, measured about epidermis and dermis part in comparison with control group. Results : NC/Nga mice suffered from dermatitis very similar to human AD with IgE hyperproduction. Specially, result that measure IgE content in serum on 8 weeks, 12 weeks, 16 weeks decreased remarkably than control group. After experiment end, result that observe revelation CD3e+/CD69+, CD4+/CD8+ and CD4+/CD25+ marker in PBMC, spleen and DLN establishment observed recover as normal with political background. And decreased than result control group which measure IL-4, IL-6, $TNF-{\alpha}$, IgG2b, IgM, IgG2a, IgG1 level in serum, and $IFN-{\gamma}$ production secreted in Th1 cell displayed increase by KCSYJT medicines. Ear thickness decrease than control group in result that observe effect that get in ear of a NC/Nga mouse. Course inflammation immunocyte etc.. permeated of result that effect that KCSYJT medicines get to NC/Nga mouse's skin establishment analyzes ear, DLN and neck-back skin after biopy, and dye by H&E, and toluidine staining (mast cells marker) method decreased about epidermis. and inflammation of dermis part remarkably than control group. Immunohistochemical examination of the skin lesion showed decrease by KCSYJT medicines on numbers of mast cells (CCR3) and CD4+ T cells containing IL-4 necessary for IgE. Conclusions : Th1 cell and Th2 cell was observed to be shift by secretion amount of IL-4 and $IFN-{\gamma}$ by KCSYJT medicines. Therefore, the KCSYJT medicine turned out to be useful in allergy autoimmune disease.

• IMMUNE NETWORK
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• 제8권3호
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• pp.90-97
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• 2008

Background: Hypersensitivity pneumonitis (HP) comprises a group of lung diseases resulting from repeated inhalation of various antigens such as Saccharopolyspora rectivirgula (SR). HP is categorized as a Th1 disease. Therefore, it has been suggested that IL-4, Th2 type cytokine, plays a protective role in the development of HP. However, the functional role of IL-4 in HP has not been extensively investigated in vivo. Therefore, we investigated the functional role of IL-4 in HP using IL-4 knockout (KO) mice. Methods: HP was induced by repeated exposure to SR in C57BL/6 (B6) and IL-4 KO (C57BL/6 background) mice. Results: IL-4 KO mice aggravated HP in terms of histological alteration, SR-specific immune responses, and inflammatory cell infiltration in the lungs compared with B6 mice. IL-4 KO mice produced high levels of IFN-${\gamma}$, TGF-${\beta}$ and TNF-${\alpha}$ in the lungs, whereas B6 mice showed the enhanced production of IL-4. Moreover, chemokines such as MIP-1${\alpha}$, MCP-1, and RANTES were highly expressed in IL-4 KO mice. IFN-${\gamma}$-secreting CD4, CD8 T cells, and neutrophils were enhanced in the bronchoalveolar lavage fluid (BALF) of IL-4 KO mice than those of B6 mice. The administration of recombinant(r) IL-4 restored these immunologic parameters in IL-4 KO mice. Conclusion: These results indicate that IL-4 plays a suppressive role in SR-induced HP by attenuating Th1-dominant immune responses.

• BMB Reports
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• 제52권4호
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• pp.289-294
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• 2019

The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with $2{\times}10^8$ colony-forming units of B. henselae Houston-1 on day 0 and subsequently on day 10. Blood and tissue samples of the mice were collected 8 days after the final B. henselae injection. B. henselae infection in the liver of Ahnak-knockout and wild-type mice was confirmed by performing polymerase chain reaction, with Bartonella adhesion A as a marker. The proportion of B. henselae-infected cells increased in the liver of the Ahnak-knockout mice. Granulomatous lesions, inflammatory cytokine levels, and liver enzyme levels were also higher in the liver of the Ahnak-knockout mice than in the liver of the wild-type mice, indicating that Ahnak deletion accelerated B. henselae infection. The proportion of CD4+interferon-${\gamma}$ ($IFN-{\gamma}^+$) and $CD4^+$ interleukin $(IL)-4^+$ cells was significantly lower in the B. henselae-infected Ahnak-knockout mice than in the B. henselae-infected wild-type mice. In vitro stimulation with B. henselae significantly increased $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, $IL-1{\alpha}$, $IL-1{\beta}$, IL-6, IL-10, RANTES, and tumor necrosis $factor-{\alpha}$ secretion was significantly elevated in the splenocytes obtained from both B. henselae-infected wild-type and Ahnak-knockout mice. These results indicate that Ahnak deletion promotes B. henselae infection. Impaired $IFN-{\gamma}$ and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice.

• 한국식품영양과학회지
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• 제43권9호
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• pp.1317-1324
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• 2014

본 연구에서는 울금 20% 주정 추출물이 LP-BM5 MuLV에 감염된 MAIDS 모델에서 면역조절 효과를 확인하기 위해 cytokines 생산, 혈장 면역글로불린 농도, T 세포 및 B 세포의 증식능, NK 세포의 활성능을 측정하였다. 그 결과 LPBM5 MuLV 감염으로 인하여 감소된 T 세포 및 B 세포의 증식능, NK 세포의 활성능을 울금 20% 주정 추출물 식이 투여가 증가시켰으며, Th1 type cytokines(IL-2, IFN-${\gamma}$)의 생성량을 증가시키고 Th2 type cytokines(IL-4, IL-10)은 억제시킴으로써 Th1/Th2 type cytokine 발현을 조절하여 면역 항상성을 유지하는 효과를 보였다. 따라서 울금은 면역조절 효과를 가진 천연 기능성 소재로서의 가능성을 기대할 수 있다.

• 한국식품영양과학회지
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• 제36권1호
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• pp.32-42
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• 2007

본 연구의 목적은 DSS로 유발시킨 대장염 동물모델에서 생식섭취가 장관 내 면역조절에 미치는 영향에 대하여 검토해보고자 했다. 그 결과, 생식섭취가 DSS로 유발시킨 대장염에서 normal군보다 IFN-$\gamma$의 함량을 증가시키고, IL-4와 IL-10의 함량은 감소시킴이 관찰되었다. 또한, 증가된 Th1 세포의 cytokine과 감소된 Th2 세포의 cytokine은 염증이 유발된 후, 생식을 통한 치료로써 변환시킬 수 있음을 증명하였다. 이러한 연구 결과를 볼 때 DSS로 유발시킨 대장염에서 생식 섭취를 통한 치료는 IL-4와 IL-10과 같은 염증성 cytokine의 억제기능을 통하여 면역시스템을 강화시키고, 손상된 염증을 완화시켜 줄 것으로 판단된다. 생식의 면역조절에 관한 자세한 기전은 아직 밝혀져 있지 않지만, 염증성 장질환에서 생식섭취가 면역학적 역할에 대한 새로운 양상들에 대한 연구가 더욱더 필요할 것으로 사료된다.

• 동의생리병리학회지
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• 제21권4호
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• pp.1017-1024
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• 2007

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via $CCR4^+$ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and $I{\kappa}B{\alpha}$ phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-${\alpha}$ and IFN-${\gamma}$. Wogonin inhibited NF-${\kappa}B$-DNA complex, NF-${\kappa}B$ binding activity, and the phosphorylation of $I{\kappa}B{\alpha}$ in a dose dependent manner. Wogonin also inhibited the translocation of NF-${\kappa}B$ from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-${\alpha}$ and IFN-${\gamma}$-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-${\kappa}B$ activation by $I{\kappa}B{\alpha}$ degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

• IMMUNE NETWORK
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• 제13권1호
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• pp.34-41
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• 2013

Interleukin-18 (IL-18) has been known to induce interferon-${\gamma}$ (IFN-${\gamma}$) production and promote Th1 immunity. Although mammalian IL-18 has been characterized in great detail, the properties and application of chicken IL-18 remain largely uninvestigated as of yet. In this study, we evaluated the immunomodulatory properties of Salmonella enterica serovar Typhimurium expressing chicken interleukin-18 (chIL-18) on immune responses induced by avian influenza (AI) and Newcastle disease (ND) vaccines. After oral administration of S. enterica serovar Typhimurium expressing chIL-18, chickens were vaccinated intramuscularly with the recommended dose of either inactivated AI H9N2 vaccine or ND (B1 strain) vaccine. Chickens receiving a primary vaccination were boosted using the same protocol 7 days later. Humoral and cell-mediated immune responses were evaluated in terms of HI antibody titers and proliferation and mRNA expression of IFN-${\gamma}$ and IL-4 of peripheral blood mononuclear cells (PBMC) in response to specific antigen stimulation. According to our results, oral administration of S. enterica serovar Typhimurium expressing chIL-18 induced enhanced humoral and Th1-biased cell-mediated immunity against AI and ND vaccines, compared to that of chickens received S. enterica serovar Typhimurium harboring empty vector. Therefore, we conclude that our proposed vaccination regimen using inactivated AI and ND viruses along with oral administration of S. enterica serovar Typhimurium expressing chIL-18 may provide a novel approach in protecting chicken from currently circulating AI and ND virus strains.