• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5767-5772
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• 2014

Background and Aim: B7-H1, a co-inhibitory molecule of the B7 family, is found aberrantly expressed in ovarian cancer cells and infiltrating macrophage/dendritic-like cells, and plays a critical role in immune evasion by ovarian cancer. IL-12, an inducer of Th1 cell development, exerts immunomodulatory effects on ovarian cancer. However, whether IL-12 regulates B7-H1 expression in human ovarian cancer associated-macrophages has not been clarified. Therefore, we investigated the effects of IL-12 on the expression of B7-H1 in ovarian cancer-associated macrophages and possible mechanisms. Methods: PMA induced THP-1-derived macrophages or human monocyte-derived macrophages were treated with recombinant IL-12 (rIL-12) or infected with adenovirus carrying human IL-12 gene (Ad-IL-12-GFP) for 24 h, then cocultured with the SKOV3 ovarian cancer cell line for another 24 h. Macrophages were collected for real-time PCR and Western blot to detect the expression of B7-H1, and activation of the NF-${\kappa}B$ signaling pathway. Moreover, supernatants were collected to assay for IL-12, IFN-${\gamma}$ and IL-10 by ELISA. In addition, monocyte-derived macrophages treated with IFN-${\gamma}$ were cocultured with SKOV3 and determined for the expression of B7-H1. Furthermore, the expression of B7-H1 in monocyte-derived macrophages was also evaluated after blocking NF-${\kappa}B$ signaling. Results: The expression of B7-H1 was significantly upregulated in monocyte-derived macrophages treated with rIL-12 or Ad-IL-12-GFP compared with the control groups (p<0.05), accompanied by a remarkable upregulation of IFN-${\gamma}$ (p<0.05), a marked downregulation of IL-10 (p<0.05) and activation of NF-${\kappa}B$ signaling. However, the upregulation of B7-H1 was inhibited by blocking the NF-${\kappa}B$ signaling pathway (p<0.05). Expression of B7-H1 was also increased (p<0.05) in monocyte-derived macrophages treated with IFN-${\gamma}$ and cocultured with SKOV3. By contrast, the expression of B7-H1 in THP-1-derived macrophages was significantly decreased when treated in the same way as monocyte-derived macrophages (p<0.05), and IL-10 was also significantly decreased but IFN-${\gamma}$ was almost absent. Conclusions: IL-12 upregulates the expression of B7-H1 in monocyte-derived macrophages, which is possible though inducing the secretion of IFN-${\gamma}$ and further activating the NF-${\kappa}B$ signal pathway. However, IL-12 downregulates the expression of B7-H1 in THP-1-derived macrophages, associated with a lack of IFN-${\gamma}$ and inhibition of expression of IL-10.

• 생명과학회지
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• 제19권4호
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• pp.514-519
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• 2009

혈관벽에 단핵구, 대식세포 등의 세포와 지질 등의 축적은 중요한 동맥경화 발병 요인이다. 이들 세포의 혈관벽으로의 이동에 있어서 chemokine인 MCP1이 중요한 역할을 한다는 것이 많이 알려져 있다. 본 연구에서는 사람 평활근세포에서 $IL-1{\beta}$의 처리에 의하여 MCP1의 발현이 증가되는 기전을 알아보고자 실험을 진행하였다. $IL-1{\beta}$의 처리는 전사인자 $NF-{\kappa}B$의 활성화를 통해 MCP1 발현을 전사단계에서 증가시켰다. 이러한 $IL-1{\beta}$에 의해 증가된 MCP1 발현을 억제하는 물질을 찾기 위해 여러 항염증작용을 하는 물질들을 전처리하여 확인해 본 결과 luteolin이 선택적으로 $IL-1{\beta}$에 의해 증가된 MCP1의 발현을 전사단계에서 저해하는 것을 확인하였고 이는 전사인자 $NF-{\kappa}B$가 핵으로 이동하는 것을 감소시킴으로써 나타나는 현상임을 확인하였다. Luteolin이 염증작용을 조절하는데 있어서 중요한 전사인자인 $NF-{\kappa}B$의 활성을 조절한다는 것을 본 실험을 통해 알 수 있었고 이는 식용식물에서 일반적으로 발견되는 luteolin이 어떠한 기전으로 항 염증작용을 하는지에 대한 이해를 높여줄 것이다.

• BMB Reports
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• 제50권12호
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• pp.640-646
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• 2017

Regulatory B cells, also well-known as IL-10-producing B cells, play a role in the suppression of inflammatory responses. However, the epigenetic modulation of regulatory B cells is largely unknown. Recent studies showed that the bromodomain and extra-terminal domain (BET) protein inhibitor JQ1 controls the expression of various genes involving cell proliferation and cell cycle. However, the role of BET proteins on development of regulatory B cells is not reported. In this study, JQ1 potently suppressed IL-10 expression and secretion in murine splenic and peritoneal B cells. While bromodomain-containing protein 4 (BRD4) was associated with $NF-{\kappa}B$ on IL-10 promoter region by LPS stimulation, JQ1 interfered the interaction of BRD4 with $NF-{\kappa}B$ on IL-10 promoter. In summary, BRD4 is essential for toll like receptor 4 (TLR4)-mediated IL-10 expression, suggesting JQ1 could be a potential candidate in regulating IL-10-producing regulatory B cells in cancer.

• 대한한의학회지
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• 제25권2호
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• pp.51-66
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• 2004

Objectives : To evaluate experimentally the clinical effect of Bojeongjeongcheon-tang, we observed the cytokines ($IL-1{\beta}$/TEX>, IL-4, IL-5, IL-6, IL-10, TNF-{\alpha},{\;}TGF-{\beta},{\;}IFN-{\gamma}$) and what effect they have on IgE in B cells of a rat. Methods : First of all, we extracted the spleens of healthy Balb/c mice and separated B cells from them. These B cells were cultured with anti-CD40 mAb (500 ng/ml), rmIL-4 (500 U/ml), Bojeongjeongcheon-tang (100 ug/ml, 10 ug/ml, 1 ug/ml). We used rmiL-10 (50 ng/ml) as a control group. Furthermore, we analyzed the expression of IgE, CD23, CD69 and the coherence of HRF in B cells using a flow cytometer. We also analyzed the cytokine gene expression in B cells by reverse transcriptase-PCR. We also measured B cells proliferation using the Liquid Scintillation Counter. Results : In this study, the Bojeongjeongcheon-tang treated group showed a tendency to decrease depending on the density compared with the control group in the expression of IgE+, CD23+, CD69, HRF. All of the Bojeongjeongcheon-tang treated group showed inhibitory effects with $IL-1{\beta}$, IL-4, IL-5 and proliferating effects with IL-6, IL-10, and $IFN-{\gamma}$ on cytokines transcript expression depending on the density. Meanwhile, $TNF-{\alpha}$ increased in all density. In IgE production, there was inhibitory effect on Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml) of significance (p < 0.01, p < 0.05). Also in B cell proliferation, the result revealed an inhibitory effect of Bojeongjeongcheon-tang (both 100 ug/ml and 10 ug/ml), of significance (p < 0.001, p < 0.01). Conclusions : This study shows that Bojeongjeongcheon-tang has an inhibitory effect on the production and activity of B cells. Also it inhibited CD23, IL-4 activity and IgE production and activation. It is obvious that Bojeongjeongcheon-tang treats asthma by inhibiting the production of histamine and HRF, IL-5 and proliferating IL-10. Also Bojeongjeongcheon-tang has some preventive effects on bronchial change by inhibiting $TGF-{\beta}$, which stimulates the bronchial transformation.

• 혜화의학회지
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• 제13권2호
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• pp.131-146
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• 2004

In the present study, we exarnined anti-allergic effect of SGBHB in cultured B cells. B cells were prepared from isolated murine splenocytes and activated by co-treatment of anti-CD40 monoclonal antibody and recombinant IL-4 allergens. Anti-allergic effects of SGBHB in activated B cells were determined by measuring B cell surface activated molecules (CD23+ and CD11a+), and expression levels of IL-$1{\beta}$, IL-6, IL-10, TNF-$\alpha$, IgE, and HRF. The major findings are summarized as follows. 1. SGBHB treatment did not produce significant cytotoxic effects on mouse lung fibroblast cells. 2. SGBHB produced significant inhibitory effect on the expression of B cell surface activated molecules (CD23+ and CD11a) in activated B cells. 3. SGBHB treatment significantly inhibited expression levels of IL-$1{\beta}$, IL-6, and TNF-$\alpha$ mRNAs in activated B cells.IL-6 protein levels were significantly decreased by $100{\mu}g/m{\ell}$ of SGBHB treatrrient, and TNF-$\alpha$ protein levels were decreased compared to the control group, but statistically insignificant. 4. SGBHB treatment significantly increased IL-10 at both mRNA and protein levels in activated B cells. 5. SGBHB treatment significantly inhibited levels of IgE production. Thus, the present data suggest that SGBHB has an anti-allergic effect on activated B cells by controlling irnmune responses, and further implicates the possibility on clinical application as a therapeutic agent.

• The Korean Journal of Physiology and Pharmacology
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• 제71권1호
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• pp.155-165
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• 2020

Ataxia telangiectasia (A-T) is an inherited neurodegenerative disease caused by mutation in the ataxia telangiectasia mutated (ATM) gene, leading to loss of function in the encoded protein ATM. Because ATM functions to reduce oxidative stress by up-regulating antioxidant enzymes, oxidative stress is a prevalent A-T phenotype and a mediator of the inflammation that drives A-T pathology. Reactive oxygen species (ROS) levels and the expression of pro-inflammatory cytokine interleukin-8 (IL-8) were higher in A-T cells than in normal cells. ROS are related to mitochondrial dysfunction and activation of nuclear factor kappa B (NF-κB) to induce IL-8 expression. Alpha-lipoic acid (α-LA), a naturally occurring thiol compound, shows an antioxidant effect in various cells. This study is aimed to determine if α-LA confers protection against NF-κB activation, IL-8 expression, and mitochondrial dysfunction in A-T cells which are exposed to the inflammatory cytokine IL-1β. A-T fibroblasts were treated with or without α-LA. The levels of intracellular and mitochondrial ROS, mRNA and protein levels of IL-8, mitochondrial membrane potential (MMP), ATP levels, and DNA binding activity of NF-κB were determined. As a result, IL-1β increased NF-κB activation, IL-8 expression, intracellular and mitochondrial ROS levels, but decreased MMP and ATP level in A-T cells. Pretreatment of A-T cells with α-LA inhibited IL-1β-induced activation of NF-κB, IL-8 expression, and mitochondrial dysfunction by reducing ROS levels. In conclusion, supplementation with α-LA may be beneficial for reducing the oxidative stress-induced mitochondrial dysfunction and IL-8 production associated with A-T.

• 동의생리병리학회지
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• 제17권4호
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• pp.1065-1074
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• 2003

In order to evaluate the antiallergic effects of Kamiyukgunja-tang (KYGJT), studies were done. We measured the cytotoxic activity for lung fibroblast cell, cytokines transcript expression, production of INF-γ, IL-10, IL-4, GM-CSF, IL-1 β, TNF-α. IL-5 proliferation of B cell in anti-CD40mAb plus r1L-4 stimulated murine splenic B cells. The results were obtained as follows : 1. KYGJT was not showed cytotoxicity in the fibroblast lung cell. 2. KYGJT increased the gene synthesis of INF-γ, IL-10, GM-CSF(m-RNA). 3. KYGJT decreased the gene synthesis of IL-1β, IL-4, TNF-α, IL-5(m-RNA). 4. KYGJT decreased the appearance of TNF-α significantly. 5. KYGJT decreased the appearance of IgE significantly. 6. KYGJT decreased the proliferation of B cell significantly. 7. KYGJT decreased the appearance of Histamin Release Production significantly. The facts above prove that KYGJT is effective against the allergy. Thus. I think that we should study on this continuously

• 대한한방종양학회지
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• 제5권1호
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• pp.103-118
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• 1999

The activity of N-acetylglucosamitnyltransferase(GnT) III and V on a Melanoma B-16 was examined after incubation with interleukin 1 (IL-1). While augumenting cell proliferation, IL-1 resulted in a decrease of GnT-III activity and an increase of GnT-V activities. Consistant with this, Melanoma B-16 cultured with IL-1 showed increased affinlity to Daturam stramonium lectin, which recognizes asialo-tri- and asialeo-tetra-antenery N-linked oligosaccharides. These results indicate that IL-1 modulate glycosyltransferase activity and the oligosaccharide structure of target cells. On the other hand, to investigate whether or not TKM-SG affect GnT-V gene expression in lung metastatic carcinoma, we used RT-PCR methods. TKM-SG treated cell lines showed low levels of secretion of GnT-V mRNA transcription as elucidated by RT-PCR. Thus, with together lower GnT-V activity levels in the medium, TKM-SG was highly effective for lung cancer metastasis treatment and it was concluded that the medicine can be used as a potent anti-lung cancer metastasis medicine.

• Toxicological Research
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• 제20권4호
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• pp.299-305
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• 2004

Adult periodontitis (AP) is a chronic inflammatory disease whose etiology is not well defined. Some studies suggested that the clinical characteristics of this disease may be in part explained by genetic factors, and some attempts to find genetic markers for this disease were successful. The interleukin-1 (IL-1) gene family as one of genetic factors may influence the expression of adult periodontitis. The aim of present study is to investigate the frequencies of genetic polymorphisms in the IL-1 gene family encoding three genes (IL-1A, IL-1B and IL-1RN) in Korean AP patients and periodontically healthy controls. There were no significant differences in genotype and allele frequencies of these polymorph isms between two groups, respectively. However, -511 polymorphism of IL-1 B gene was significantly associated with mean pocket depth (MPD, mm) value in AP patients (P<0.05). Therefore, our results suggest that -511 polymorphism in the IL-1B gene may be useful as a genetic marker for the severity of AP in Koreans.

• 한국자원식물학회지
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• 제33권6호
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• pp.659-665
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• 2020

Adenophorae Radix (AR) has been used as a traditional medicine for various diseases. However, the regulatory mechanisms of AR in allergic inflammation are not yet understood. The present study was conducted to investigate the effect and mechanisms of AR on the mast cell-mediated allergic response. To determine the pharmacological mechanisms of AR in allergic inflammation, we evaluated the effects of AR on the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-8 as well as the activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). Our results demonstrated that AR effectively attenuated the PMACI-induced production of TNF-α, IL-6, IL-1β and IL-8 in stimulated HMC-1. Additionally, we showed that the inhibitory effect of AR on inflammatory cytokines in PMACI-stimulated HMC-1 cells involved the suppression of the activation NF-kB/caspase-1 in PMACI-stimulated HMC-1. Collectively, these findings provide experimental evidence that AR may be a useful candidate for the treatment of allergic inflammation.