• BMB Reports
• /
• 제52권9호
• /
• pp.548-553
• /
• 2019

Ets-1 is a prototype of the ETS protein family. Members of the ETS protein family contain a unique ETS domain. Ets-1 is associated with cancer progression and metastasis in many types of cancer. Many studies have shown a link between elevated expression of Ets-1 in cancer biopsies and poor survival. CCR7 is a chemokine that binds to specific ligand CCL21/CCL19. CCR7 expression is associated with tumor metastasis and infiltration into lymph nodes. The objective of this study was to test whether Ets-1 could regulate CCR7 expression and enhance tumor metastasis. Our data showed that CCR7 expression was downregulated in Ets-1-deficient T cells upon T-cell stimulation. Overexpression of Ets-1 increased CCR7 expression in breast cancer cell lines. In contrast, knockdown of Ets-1 reduced CCR7 expression. Ets-1 could directly bind to CCR7 promoter and mediate CCR7 expression in luciferase reporter assays and chromatin immunoprecipitation assays. Transactivation activity of Ets-1 was independent of the Pointed domain of Ets-1. Ets-1 could also enhance $NF-{\kappa}B$ and CBP transactivation of CCR7 promoter. Our results also showed that Ets-1 could modulate cancer cell transmigration by altering CCR7 expression in transwell assay and wound healing assay. Taken together, our data suggest that Ets-1 can enhance CCR7 expression and contribute to tumor cell migration.

• Biomolecules & Therapeutics
• /
• 제29권2호
• /
• pp.154-165
• /
• 2021

This study aimed to investigate whether the antidiabetic drugs dipeptidyl peptidase 4 (DPP4) inhibitors such as evogliptin and sitagliptin affect the membrane DPP4 (mDPP4) enzymatic activity and immune function of T helper1 (Th1) cells in terms of cytokine expression and cell profiles. The mDPP4 enzymatic activity, cytokine expression, and cell profiles, including cell counts, cell viability, DNA synthesis, and apoptosis, were measured in pokeweed mitogen (PWM)-activated CD4+CD26+ H9 Th1 cells with or without the DPP4 inhibitors, evogliptin and sitagliptin. PWM treatment alone strongly stimulated the expression of mDPP4 and cytokines such as interleukin (IL)-2, IL-10, tumor necrosis factor-alpha, interferon-gamma, IL-13, and granulocyte-macrophage colony stimulating factor in the CD4+CD26+ H9 Th1 cells. Evogliptin or sitagliptin treatment potently inhibited mDPP4 activity in a dose-dependent manner but did not affect either the cytokine profile or cell viability in PWM-activated CD4+CD26+ H9 Th1 cells. These results suggest that, following immune stimulation, Th1 cell signaling pathways for cytokine expression function normally after treatment with evogliptin or sitagliptin, which efficiently inhibit mDPP4 enzymatic activity in Th1 cells.

• IMMUNE NETWORK
• /
• 제4권1호
• /
• pp.31-37
• /
• 2004

Background: 1-8D gene is a member of human 1-8 interferon inducible gene family and is shown to be overexpressed in fresh colon cancer tissues. Three peptides 1-6, 3-5 and 3-7 derived from 1-8D gene were shown to have immunogenicity against colon cancer. Methods: To study tumor immunotherapy of these peptides we established an adoptive transfer model. $D^{b-/-}{\times}{\beta}2$ microglobulin (${\beta}2m$) null mice transgenic for a chimeric HLA-A2.1/$D^b-{\beta}2m$ single chain (HHD mice) were immunized with irradiated peptide-loaded RMA-S/HHD/B7.1 transfectants. Spleens were removed after last immunization, and splenocytes were re-stimulated in vitro. Lymphocytes from vaccinated HHD mice were transferred together with IL-2 to the tumor bearing nude mice that were challenged S.C. with the HCT/HHD/B7 colon carcinoma cell line that was found to grow in these mice. Results: Peptide 3-5 was found to be highly effective in CTL activity. Adoptively transferred anti-peptide 3-5 cytolytic T lymphocytes caused significant retardation in tumor growth. Conclusion: This study shows that peptide 3-5 can be the most effective candidate for the vaccine of adoptive immunotherapy against colon cancer.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제41권
• /
• pp.56.1-56.6
• /
• 2019

Background: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. Methods: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. Results: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. Conclusion: The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

• Tuberculosis and Respiratory Diseases
• /
• 제47권2호
• /
• pp.161-171
• /
• 1999

연구배경: Interleukin-12 (IL-12) 는 자연살해세포와 T 림프구 활성을 증가시킬 뿐 아니라 증식을 촉진시키고 mterferon-$\gamma$와 granulocyte-macrophage colony stimulating factor 그리고 tumor necrosis factor-$\alpha$ (TNF-$\alpha$)의 생성을 유도한다고 알려져 있으며 여러 동물실험에서 악성종양의 치료에 상당한 효과가 있음이 알려져 있다. 이런 결과는 종양내 염증세포의 침윤이 증가함과 밀접한 관련이 있다고 밝혀져 있지만 이들 염증세포가 종양내로 이동하는 단계에 IL-12가 미치는 영향에 대해서는 잘 알려진 바가 없다. 본 연구에서는 IL-12가 종양의 성장 및 전이에 미치는 영향과 활성화된 내피세포에 발현되는 것으로 알려진 E-selectin의 발현에 미치는 영향을 관찰하고자 하였고 또한 E-selectin의 발현이 IL-12에 의해 생산이 증가되고 여러 유착분자의 발현을 유도하는 작용이 있는 것으로 알려진 TNF-$\alpha$와 연관이 있는지 알아보고자 하였다. 방법: C57BL/6 마우스를 대상으로 Lewis 폐암세포주를 피하주사하여 암세포를 이식한 후 각 군마다 각각 IL-12 또는 TNF-$\alpha$ 생리식염수를 복강내 투여하였다. 암세포이식 28일째 마우스를 도살하여 폐전이 결절의 수를 측정하였으며 피하종양에 대해 CD4, CD8, CD16, E-selectin에 대한 면역화학조직염색을 시행 하였다. 결과: IL-12를 투여한 군에서 대조군에 비해 암세포 이식부위의 종양 크기가 감소하였으며 폐전이 결절의 수도 감소하였다. IL-12를 투여한 군에서 대조군에 비해 CD4+ 및 CD8+ 그리고 CD16+ 세포의 종양내 침윤이 증가하였다. IL-12를 투여하지 않은 대조군에서 E-selectin은 발현되지 않았으나 IL-12 투여군에서 종양내 혈관내피세포에서의 E-selectin 발현이 증가되었다. TNF-$\alpha$ 투여시 종양내 혈관내피세포에서의 E-selectin 발현 증가가 관찰되었으며 또한 종양내 CD4+ 및 CD8+ 그리고 CD16+ 세포의 침윤이 증가되었다. 결론: 이상의 결과로 보아 IL-12는 Lewis 폐암모델에서 종양내 염증세포의 침윤을 일으켜 종양의 성장과 전이를 억제하는 작용을 나타내며 염증세포의 침윤에는 E-selectin이 관여할 것으로 생각된다. 또한 E-selectin의 발현증가에는 IL-12 에 의해 생성이 유도되는 TNF-$\alpha$가 작용할 가능성을 추정할 수 있겠다.

• Journal of Animal Science and Technology
• /
• 제50권6호
• /
• pp.849-856
• /
• 2008

본 연구에서는 복분자(라즈베리)의 돼지 비장 임파구에 대한 면역 반응을 조사하였다. 복분자의 70% 에틸 알코올 추출물을 돼지 비장 임파구에 처리하였다. 복분자의 추출물은 비장 면역세포의 증식을 촉진하였으며, 복분자(라즈베리)의 추출물은 돼지 비장 임파구에 대해 CD3-T 세포, CD4-T 세포와 B 세포의 구성분을 증가시켰다. 복분자 추출물은 비장 임파구 세포의 활력을 증가시킴으로써 면역반응을 향상시켰다. 본 연구에서 우리는 돼지 비장세포에 복분자 추출물을 처리한 결과 8개의 유전자 발현이 증가되었음을 확인했는데, 이들 중에는 세포구조와 면역반응에 관여하는 유전자가 포함되었다. 특히 microtubule-associated protein 4, cytoplasmic dynein heavy chain, tumor necrosis factor alpha, 및 lymphotoxin-beta receptor precursor 유전자 발현이 증가되었다. 한편 10개의 유전자는 복분자 추출물에 의해 그 발현이 감소되었다.

• 생약학회지
• /
• 제40권1호
• /
• pp.35-40
• /
• 2009

The immunomodulatory activities of the ethanol extract of Gynostemma pentaphyllum, termed hereafter as GPE, were examined in immunosuppressed mice as well as in normal mice in the present study. Oral administration of GPE into mice prevented dexamethasone (DEX)-induced immunosuppression as determined by the mitogen-induced proliferation of the splenocytes and the the cytokine production (TNF-$\alpha$, IL-$1{\beta}$) in the whole blood culture. In addition, oral administration of GPE increased antitumor host defense in mice implanted with sarcoma-180 tumor cells. The immunoaugmenting activity of orally administered GPE was also confirmed in mice immunized with ovalbumin (OVA). Mice that were orally administered with GPE generated much more potent OVA-specific cytotoxic T lymphocyte (CTL) responses upon intravenous OVA injection compared to the untreated controls. These results demonstrate that oral administration of the ethanol extract of Gynostemma pentaphyllum could be useful to increase host defense in immunocompromised situations such as stress- or tumor-induced immunosuppression.

• Journal of Microbiology and Biotechnology
• /
• 제29권9호
• /
• pp.1444-1452
• /
• 2019

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (${\gamma}-PGA$), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with ${\gamma}-PGA$ did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with ${\gamma}-PGA$ and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of ${\gamma}-PGA$ markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of $CD8^+$ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제46권1호
• /
• pp.3-11
• /
• 2020

Immunoglobulin G4 (IgG4)-related dacryoadenitis and sialoadenitis (IgG4-DS) are part of a multiorgan fibroinflammatory condition of unknown etiology termed IgG4-related disease (IgG4-RD), which has been recognized as a single diagnostic entity for less than 15 years. Histopathologic examination is critical for diagnosis of IgG4-RD. CD4+ T and B cells, including IgG4-expressing plasma cells, constitute the major inflammatory cell populations in IgG4-RD and are thought to cause organ damage and tissue fibrosis. Patients with IgG4-RD who have active, untreated disease exhibit significant increase of IgG4-secreting plasmablasts in the blood. Considerable insight into the immunologic mechanisms of IgG4-RD has been achieved in the last decade using novel molecular biology approaches, including next-generation and single-cell RNA sequencing. Exploring the interactions between CD4+ T cells and B lineage cells is critical for understanding the pathophysiology of IgG4-RD. Establishment of pathogenic T cell clones and identification of antigens specific to these clones constitutes the first steps in determining the pathogenesis of the disease. Herein, the clinical features and mechanistic insights regarding pathogenesis of IgG4-RD were reviewed.

• 동의생리병리학회지
• /
• 제33권1호
• /
• pp.17-24
• /
• 2019

Cymbopogon citratus, commonly know as lemongrass, prossesses strong antioxidant, anti-tumor and anti-inflammatory properties. Howerver, its anti-obesity activity remains to be elucidated. This study investigated the effect of ethanol extract of Cymbopogon citratus on adipogenesis, and its underlying mechanism, in 3T3-L1 preadipocytes. The results demonstrated that ethanol extracts of Cymbopogon citratus effectively suppressed intercellular lipid accumulation at non-toxic concentrations, and was associated with the down-regulation of adipocyte-specific transcription factors, including $C/EBP{\alpha}$ and $PPAR{\gamma}$, and phosphorylation of $AMPK{\alpha}$. Furthermore, ethanol extracts of Cymbopogon citratus increased p21 and p21 expression, while the expression of CDK2, cyclin A and cyclin B1 was reduced. As a result, ethanol extracts of Cymbopogon citratus seems to induce G0/G1 cell cycle arrest of 3T3-L1 cells. On the other hand, ERK and Akt signaling pathways were not involved in anti-adipogenesis by ethanol extracts of Cymbopogon citratus. Taken together, theses results suggest that ethanol extracts of Cymbopogon citratus inhibits adipocyte differentiation in 3T3-L1 cells and can be used as a safe and efficient natural substance to manage anti-obesity.