• Parasites, Hosts and Diseases
• /
• 제51권1호
• /
• pp.85-92
• /
• 2013

IL-23 and IL-12 are structurally similar and critical for the generation of efficient cellular immune responses. Toxoplasma gondii induces a strong cell-mediated immune response. However, little is known about IL-23 secretion profiles in T. gondii-infected immune cells in connection with IL-12. We compared the patterns of IL-23 and IL-12 production by THP-1 human monocytic cells in response to stimulation with live or heat-killed T. gondii tachyzoites, or with equivalent quantities of either T. gondii excretory/secretory proteins (ESP) or soluble tachyzoite antigen (STAg). IL-23 and IL-12 were significantly increased from 6 hr after stimulation with T. gondii antigens, and their secretions were increased with parasite dose-dependent manner. IL-23 concentrations were significantly higher than those of IL-12 at the same multiplicity of infection. IL-23 secretion induced by live parasites was significantly higher than that by heat-killed parasites, ESP, or STAg, whereas IL-12 secretion by live parasite was similar to those of ESP or STAg. However, the lowest levels of both cytokines were at stimulation with heat-killed parasites. These data indicate that IL-23 secretion patterns by stimulation with various kinds of T. gondii antigens at THP-1 monocytic cells are similar to those of IL-12, even though the levels of IL-23 induction were significantly higher than those of IL-12. The detailed kinetics induced by each T. gondii antigen were different from each other.

• 대한한방내과학회지
• /
• 제27권1호
• /
• pp.228-236
• /
• 2006

Objectives : Macrophage has an important innate defense role in the immune system. When we are infected with pathogens, macrophage ingests them through phagocytosis or endocytosis, and then secretes many cytokines, such as IL-1, IL-6 and $TGF{\alpha}$, which are regulators of immune responses. The aim of this study is to determine how Samjunghwan effects the expression of cytokine and other immune-related genes in macrophages. Methods : Cells were treated directly with Samjunghwan and/or LPS at regular intervals. Total RNA of cells was isolated using TRIzol reagent, and the changes in cytokine gene expressions were investigated using RT-PCR, western blot and ELISA. Results : $IL-1{\alpha},\;IL-1{\beta}$ and COX-2 genes were inducibly expressed specifically by Samjunghwan in macrophage. Especially, $IL-1{\beta}$ gene was induced most strongly by treatment with Samjunghwan. Over time, treatment with Samjunghwan showed that the expression levels of $IL-1{\alpha}\;and\;$IL-1{\beta}$ genes increased from 1 to 4h, and then decreased from 4 to ISh. However, the expression level of COX-2 gene increased continuously up to 11h. $IL-1{\alpha},\;IL-1{\beta}$ and COX-2 genes were expressed synergistically by a simultaneous treatment of both Samjunghwan and LPS in macrophages. Secretion levels of translated $IL-1{\beta}$ increased continuously up to 11h. Conclusions : Though this study is only a start in the investigation of the efficasy of Samjunghwan, these results suggest that Samjunghwan has positive effects on immune responses.

• 생명과학회지
• /
• 제19권3호
• /
• pp.411-416
• /
• 2009

본 연구에서는 키토산이 마우스에서 Th1과 Th2 사이토카인의 생성에 미치는 효과를 보기 위하여 키토산에 의한 IL-2 생성의 변화, 키토산에 의한 IFN-$\gamma$ 생성의 변화, 그리고 키토산에 의한 IL-4 생성의 변화, 키토산에 의한 IL-10 생성의 변화를 시험관내에서 시험하였다. 또한 LPS, Con A, PHA-P와 같은 세포자극물과 키토산이 함께 작용되었을 때 상기 사이토카인의 생성의 변화를 관찰하였다. 키토산을 비장세포에 노출시켰을 때 Th1 사이토카인인 IL-2와 IFN-$\gamma$의 생성이 크게 증가하였지만 고농도의 키토산에 의해서는 오히려 대조군에 비하여 감소하였다. LPS와 같은 세균독소, Con A와 같은 세포자극물을 비장세포에 노출시켰을 때 IL-2와 IFN-$\gamma$의 생성은 큰 상승을 나타냈으며 LPS의 경우 키토산에 의해서 IL-2와 IFN-$\gamma$의 생성이 증폭되었다. 키토산을 비장세포에 노출시켰을 때 Th2 사이토카인인 IL-4와 IL-10의 생성은 큰 증가를 보이지 않았다. LPS와 같은 세균독소에 의한 IL-4와 IL-10의 상승이 키토산에 의해서 억제되었다. 따라서 이러한 결과들로 부터 키토산이 LPS와 같은 세균독소가 존재하는 가운데 Th1 사이토카인을 증가시키고 Th2 사이토카인을 감소시킴에 따른 면역반응 환경이 이루어질 가능성이 높다 하겠다. 앞으로 키토산에 대한 더 많은 자료의 축적이 이루어지게 되면 임상에서 Th1/Th2 면역반응의 균형을 유지하는데 이용될 가능성도 있다 하겠다.

• IMMUNE NETWORK
• /
• 제5권1호
• /
• pp.16-22
• /
• 2005

Background: IL-18 was originally cloned as a IFN-${\gamma}$ inducing factor in primed T cells. In synergy with IL-12, IL-18 has been shown to induce strikingly high levels of IFN-${\gamma}$ production by T cells and to enhance Th1 development. Also this cytokine exerts induction of Th2 development through IL-4 induction. Methods: Resting $CD4^+$ T cells were sorted by negative selection and activated by anti-CD3 plus anti-CD28 Ab. Expression of IL-12 binding sites, IL-18 binding sites, IL-18R ${\alpha}$, and GATA-3 mRNA were analysed by FACS and RT-PCR, respectively. Results: Resting $CD4^+$ T cells expressed IL-18R ${\alpha}$ chain but not IL-18 binding sites, suggesting a lack of IL-18R ${\beta}$ expression. IL-18R ${\alpha}$ was maintained on the Th1 and Th2 committed cells. IL-18 binding sites were induced on the Th1 but not Th2 cells. Exposure of these cells to IL-18 led to up-regulation of GATA-3 mRNA expression only in Th2 committed cells. To elucidate the relationship between IL-18R ${\alpha}$ expression and GATA-3 induction by IL-18, Th1 and Th2 committed cells were further cultured in medium with or without IL-12 for 2 days. IL-12 binding sites were maintained on the Th1 and Th2 cells regardless of IL-12 treatment, but IL-18R a expression was rapidly down-regulated on the IL12-untreated Th2 cells which did not induce GATA-3 mRNA expression followed by IL-18 stimulation. Conclusion: IL-12 supports expression of IL-18R ${\alpha}$ and GATA-3 mRNA expression was induced by IL-18 through IL-18R ${\alpha}$ without expression of IL-18 binding site in Th2 cells.

• Animal cells and systems
• /
• 제13권4호
• /
• pp.391-397
• /
• 2009

The house dust mite (Dermatophagoides pteronissinus) is an important factor in triggering allergic diseases. The function of eosinophils, particularly in the production of cytokine or chemokine, is critical in understanding the pathogenesis of inflammatory diseases. In this study, we examined whether D. pteronissinus extract (DpE) induces the expression of monocyte chemotactic protein 1 (MCP-1)/CCL2, IL-8/CXCL8, and IL-6 that mediate in the infiltration and activation of immune cells and in its signaling mechanism in the human eosinophilic cell line, EoL-1. DpE increased the mRNA and protein expression of MCP-1, IL-8, and IL-6 in a time- and dose-dependent course in EoL-1 cells. In our experiments using signal-specific inhibitors, we found that the increased expression of MCP-1, IL-8, and IL-6 due to DpE is associated with Src family tyrosine kinase and protein kinase C $\delta$ (PKC $\delta$). In addition, the activation of extracellular signal-regulated kinase (ERK) is required for MCP-1 and IL-8 expression while p38 mitogen-activated protein kinase (MAPK) is involved in IL-6 expression. DpE induced the phosphorylation of ERK and p38 MAPK. PP2, an inhibitor of Src family tyrosine kinase, and rottlerin, an inhibitor of PKC $\delta$, blocked the activation of ERK and p38 MAPK. DpE induces the activation of ERK and p38 MAPK via Src family tyrosine kinase and PKC $\delta$ for MCP-1, IL-8, or IL-6 production. Increased cytokine release due to the house dust mite and the characterization of its signal transduction may be valuable in understanding the eosinophil-related pathogenic mechanism of inflammatory diseases.

• Journal of Microbiology and Biotechnology
• /
• 제31권6호
• /
• pp.794-802
• /
• 2021

In this study we investigated the role and mechanism of cardamonin on IL-1β induced injury in OA. CHON-001 cells were treated with cardamonin and IL-1β and transfected with silencing nuclear factor erythroid 2-related factor 2 (siNrf2). Cell viability was detected by Cell Counting Kit-8 assay and flow cytometer assay was utilized for cell apoptosis assessment. IL-6, IL-8, TNF-α and Nrf2 mRNA expression was tested by qRT-PCR. Western blot was employed to evaluate MMP-3, MMP-13, Collagen II, Nrf2, NQO-1, NLRP3, Caspase 1 and apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) protein levels. In CHON-001 cells, IL-1β suppressed cell viability and Collagen II level while promoting cell apoptosis and expression of pro-inflammatory cytokines (IL-6, IL-8, TNF-α), MMPs (MMP-3, MMP-13), NQO-1, and NLRP3 inflammasome (NLRP3, Caspase 1 and ASC), with no significant influence on Nrf2. Cardamonin reversed the effect of IL-1β on cell viability, cell apoptosis, pro-inflammatory cytokines, MMPs, Collagen II, and NLRP3 inflammasome levels. In addition, cardamonin advanced Nrf2 and NQO-1 expression of CHON-001 cells. SiNrf2 reversed the function of cardamonin on IL-1β-induced cell apoptosis and expression of pro-inflammatory cytokines, Nrf2, NQO-1, and NLRP3 inflammasome in chondrocytes. Taken together Cardamonin inhibited IL-1β induced injury by inhibition of NLRP3 inflammasome via activating Nrf2/NQO1 signaling pathway in chondrocyte.

• Restorative Dentistry and Endodontics
• /
• 제24권1호
• /
• pp.49-54
• /
• 1999

Ko, Lim found some differences in the concentrations of bone resorptive cytokines, especially IL-$1{\alpha}$ and IL-$1{\beta}$ in periapical lesions and inflamed pulps. And they suppose that these differences may be due to the type of cells which produce each cytokine. The purpose of this study was to analyze the human odontogenic cysts & cystic fluid for their contents of IL-$1{\alpha}$, IL-$1{\beta}$ and TNF-$1{\alpha}$ and to compare the concentrations of each cytokine according to the cytokine producing cells. The cystic tissues used in this experiment, were obtained from periapical surgery or cyst enucleation surgery. Cystic fluid was obtained from root canal during routine endodontic therapy(n=5). Cystic tissues were subdivided into two groups, inflammatory radicular cyst group(n=15) and developmental odontogenic keratocyst group(n=3). Normal periapical tissues of extracted third molar(n=5) were also obtained to be used as control group. Each specimen was incubated in 0.5ml homogenizing buffer (0.1mol/L potassium chloride, 0.02mol/L TRIS;pH=7.6) for two hours and then homogenized with glass homogenizer. Each specimen was centrifuged in a microcentrifuge for 3 minutes, and supernatants were extracted. The concentrations of cytokines were measured with R&D ELISA kit. The data were analyzed by Mann-Whitney U test for the differences among the diseases and t test for the correlations among each cytokine. Following results were obtained ; 1. For IL-$1{\alpha}$ and IL-$1{\beta}$, all experimental groups showed significantly higher concentrations of each cytokine than the control group (p<0.05). 2. In radicular cysts, the concentrations of IL-$1{\alpha}$ were higher than IL-$1{\beta}$, but not stastically significant (p>0.05). In odontogenic keratocysts, the concentrations of IL-$1{\alpha}$ were significantly higher than IL-$1{\beta}$ (p<0.05). In cystic fluid, the concentration of IL-$1{\beta}$ was significantly higher than IL-$1{\alpha}$ (p<0.05). 3. Between odontogenic keratocysts and radicular cysts, the concentrations of IL-$1{\alpha}$ were significantly higher in odontogenic keratocysts than in radicular cysts (p<0.05). 4. For TNF-${\alpha}$, only cystic fluid group showed significantly higher concentrations than the control group (p<0.05).

• 생명과학회지
• /
• 제26권9호
• /
• pp.1082-1087
• /
• 2016

본 연구에서는 염증성 사이토카인 IL-1α가 소장의 tight junction (TJ)의 integrity에 미치는 영향을 평가하고 항염증 효능이 있다고 알려진 curcumin (CCM)이 IL-1α에 의한 TJ 손상 예방효과를 알아보고자 Caco-2 세포 모델을 이용하여 실험하였다. Caco-2 세포 단층의 TJ integrity에 대한 IL-1α의 영향을 FITC-dextran flux와 transepithelial electrical resistance (TEER)를 측정하여 검증하였다. IL-1α를 100 ng/ml의 농도로 Caco-2 세포 단층의 상부에 24시간 동안 처리하였을 때 처리 2시간 이후 FITC-dextran의 flux가 유의적으로 증가하였고, IL-1α 처리시간에 비례하여 상승하였다. 또한 IL-1α의 처리는 TEER 값을 유의적으로 감소시켜 IL-1α에 의한 TJ 손상을 확인할 수 있었다. 반면 CCM의 전처리는 이러한 IL-1α에 의한 TJ 기능 저하를 거의 완전히 예방하는 것을 알 수 있었다. 이상의 결과로 염증성 사이토카인 IL-1α이 TJ의 integrity 조절에 부정적인 영향을 미치며 이는 강황에서 발견되는 CCM 전처리에 의해 효과적으로 억제될 수 있음을 보여준다. 본 연구 결과와 관련되어 TJ 구성단백질 발현 및 작용 기작에 대한 분자세포생물학적 연구와 in vivo 연구가 필요하다.

• 한국약용작물학회지
• /
• 제15권1호
• /
• pp.38-45
• /
• 2007

한국산 겨우살이 (Viscum album L)는 면역조절작용이 있음이 밝혀졌다. 본 연구에서 한국산 겨우살이 열탕추출물 M11C (non-lectin components)가 비장세포를 활성화시켜 $IL-1\beta$를 생산 분비하게 하는지를 조사하였다. 비장세포를 M11C로 자극한 후, 배양액을 수집 혹은 세포 용해물을 수거해 $IL-1\beta$ 분비와 전사량을 ELISA, immunoblotting, RT-PCR로 검사했었다. 비장세포로부터 $IL-1\beta$ 분비와 전사 효과에 있어서 M11C는 농도 의존성과 자극시간 의존성을 보였다. 비장세포로부터 최대의 $IL-1\beta$ 분비를 위한 M11C의 최대의 농도와 자극시간은 각각 $200{\mu}g/m\ell$와 8시간 이었다. 그리고 최대 $IL-1\beta$ mRNA 전사를 위한 M11C의 최대의 농도와 자극시간은 각각 $200{\mu}g/m\ell$와 4시간 이었다. 최대의 전사시간은 최대의 분비시간보다 4시간 빨리 도달된 것으로 나타났다. 이러한 최대의 $IL-1\beta$ 분비효과가 당분해효소인 Viscozyme L에 의해 완전히 저해되었다. 이는 M11C (non-lectin components)의 구성물질 들 중 다당체 혹은 올리고당들이 $IL-1\beta$ 생산 분비를 유도하는 주된 물질임을 말해주고 있다.

• 정신신체의학
• /
• 제10권2호
• /
• pp.130-141
• /
• 2002

스트레스가 위장관 기능을 변화시키며 이에는 interleukin과 시상하부-뇌하수체-부신피질 축이 관여한 다고 알려져 있다. 한편 우울증이 기능성 위장관 장애 및 interleukin과 연관성을 지닌다. 본 연구에서는 IL-$1\beta$, IL-2, IL-6의 혈청 농도를 기능성 위장관 장애 환자에서 측정하고, 혈청 cortisol 및 우울증과 스트레스의 정도를 조사하여 기능성 위장관 장애에 있어서 interleukin의 역할과 우울증 및 스트레스와의 상관성을 살펴보고자 하였다. 방법: 기능성 위장관 장애의 진단을 위한 로마기준 II에 따라 진단된 환자 20명과 건강한 대조군 20명을 대상으로 하였다. 채취한 혈액에서 혈청을 분리한 다음 Enzyme-linked Immunosorbent Assay 방법으로 혈청 IL-$1\beta$, IL-2, IL-6 농도를 측정하고 Fluorescence Polarization Immunoassay 방법으로 혈청 cortisol 농도 를 측정하였다. 우울증상의 정도를 Hamilton Rating Scale for Depression을 이용하여 평가하고, Schedule of Recent Experience를 이용하여 최근 일년간의 스트레스 생활사건의 양을 측정하여 비교하였다. 결과는 다음과 같다. 결과: 1) 기능성 위장관 장애 환자들의 혈청 IL-$1\beta$, IL-2 농도는 대조군에 비해 유의하게 낮았으나 혈청 IL-6 농도는 차이가 없었다. 2) 기능성 위장관 장애 환자군의 혈청 cortisol 농도는 대조군에 비해 유의하게 높았고, 우울증상도 유의하게 더 심하였으며, 스트레스 생활사건의 양 또한 유의하게 더 많았다. 3) 기능성 위장관 장애에서 우울증상의 정도와 혈청 cortisol 간에는 유의한 정상관관계가 있었다. 정도는 IL-$1\beta$와 역상관하는 경향이 있고, IL-2와는 정상관하였다. 스트레스 생활사건의 양파 혈청 cortisol 농도는 IL-6 와 유의하게 정상관하였다 대조군을 포함한 전 집단에서 IL-$1\beta$는 우울 정도, 스트레스 생활사건의 양, 혈청 cortisol 등과 유의하게 역 상관하였다. IL-6와 의하게 정상관하였다. 결론: 기능성 위장관 장애는 우울증 및 스트레스와 연관되며, 우울증, 스트레스가 심할수록 혈청 cortisol이 높았다. 기능성 위장관 장애 환자들에서 IL-$1\beta$, IL-2가 감소되어 있었지만, IL-6는 변화가 없었다. 상대적으로 증가된 혈청 cortisol이 IL의 변화와 관련될 수 있다고 생각된다.