• KSBB Journal
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• 제28권6호
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• pp.415-422
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• 2013

Gamma irradiation (${\gamma}IR$) is widely used for radiotherapy as a treatment of cancer cells although it has a risk to damage normal cells. Inflammation is regarded as one of side effects of ${\gamma}IR$ while the effect of low dose of ${\gamma}IR$ on inflammation has not been researched well. Here, we investigated the inflammatory responses of low dose of ${\gamma}IR$ on murine spleen cells. It was evaluated if ${\gamma}IR$ affected the mitogen-induced lymphocyte proliferation, the regulation of various inflammatory cytokines (IFN-${\gamma}$, IL-2, IL-17, IL-4, IL-10), and the involvement of Ikaros and MAPK/NF-${\kappa}B$ medicated mechanism. Exposure of $^{137}Cs-{\gamma}IR$ below 2 Gy decreased the lymphocytes proliferative response to mitogens (LPS, ConA) except at the lowest dose, 0.05 Gy. IL-17, IL-2 and IL-4 mRNA increased at 0.5 and 2 Gy, but not altered at 0.05 Gy. IL-10, anti-inflammatory cytokine, increased only at 0.05 Gy. In regard to intracellular signaling, p-JNK, p-p38 and p-$I{\kappa}B{\alpha}$ were not changed, whereas the activation of ERK and Ikaros increased at the lowest dose. These results suggest that exposure of ${\gamma}IR$ less than 0.5 Gy (or below 0.05 Gy) has beneficial effects as a radiation hormesis on immune function.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.3955-3960
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• 2012

Objective: To investigate the effects of $CD4^+$, IL17 and Foxp3 expression on prognosis of operable non-small cell lung cancer (NSCLC) with different pTNM stages. Methods: Expression of $CD4^+$, IL17 and Foxp3 in 102 cases of NSCLC tissues and adjacent cancer tissues was detected by immunohistochemistry and associations with prognosis with different pTNM stages were analyzed. The Chi-square test was used to compare count data. Survival differences were evaluated by Kaplan-Meier single factor analysis and the COX regression model was used to analyze the relationship between influential factors and the disease prognosis. The significance level was ${\alpha}$=0.05. Results: Expression of CD4, IL-17 and Foxp3 significantly varied in different pTNM stages of NSCLC tissues (P < 0.05). The same was true for CD4 expression (P < 0.05). The median survival time (MST) in the positive CD4 expression group was evidently higher than that in the negative group (25.8/23.9 months). Compared with stage III, the MST difference of stages I and II in the positive CD4 expression group were statistically significant (P < 0.05). The MST in positive IL-17 and Foxp3 expression groups was obviously lower than that in the corresponding negative group (P < 0.05) (25.6/35.1 months and 24/35.3 months, respectively). There was a significant difference of MST between any two of three stages of positive IL-17 expression group (P < 0.05), and it was the same with positive Foxp3 expression group. TNM stage, negative CD4 expression, and positive IL-17 and Foxp3 expression were the main risk factors for the prognosis of NSCLC. Conclusion: Surgical prognosis of NSCLC can be better assessed by the combination of clinical staging and expression of IL17 and Foxp3.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.466-473
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• 2019

Angelica gigas has been used as a Korean traditional medicine for pain relief and gynecological health. Although the extracts are reported to have an anti-inflammatory property, the bioactive compounds of the herbal plant and the effect on T cell responses are unclear. In this study, we identified decursinol angelate (DA) as an immunomodulatory ingredient of A. gigas and demonstrated its suppressive effect on type 17 helper T (Th17) cell responses. Helper T cell culture experiments revealed that DA impeded the differentiation of Th17 cells and IL-17 production without affecting the survival and proliferation of CD4 T cells. By using a dextran sodium sulfate (DSS)-induced colitis model, we determined the therapeutic potential of DA for the treatment of ulcerative colitis. DA treatment attenuated the severity of colitis including a reduction in weight loss, colon shortening, and protection from colonic tissue damage induced by DSS administration. Intriguingly, Th17 cells concurrently with neutrophils in the colitis tissues were significantly decreased by the DA treatment. Overall, our experimental evidence reveals for the first time that DA is an anti-inflammatory compound to modulate inflammatory T cells, and suggests DA as a potential therapeutic agent to manage inflammatory conditions associated with Th17 cell responses.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.291-297
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• 2015

The Homeobox B13 (HOXB13):Interleukin 17 Receptor B (IL17BR) index of estrogen receptor (ER)-positive breast cancer (ER (+) BC) patients may be a potential biomarker of recurrence/ metastasis. However, effects of microRNA (miRNA) binding to the 3' untranslated region (3' UTR) of HOXB13 and IL17BR and its function on recurrence/metastasis in ER (+) BC remains elusive. The aims of this study were to determine the expression of miRNAs that bind to 3' UTR of HOXB13 and IL17BR in ER (+) BC patients and asess the effects of these miRNAs on recurrence/metastasis. The expression profiles of HOXB13 and IL17BR were evaluated using RT-PCR in tumors and normal tissue samples from 40 ER (+) BC patients. The expression level of 4 miRNAs, which were predicted to bind the 3' UTR of HOXB13 and IL17BR using TargetScan, microRNA.org and miRDB online databases, were further evaluated with RT-PCR. Our findings demonstrated that high miR-1266 levels might be significant prognostic factor for recurrence/metastasis occurrence (3.05 fold p=0.004) and tamoxifen response (3.90 fold; p=0.2514) in ER (+) BC cases. Although we suggest that modulation of miR-1266 expression may be an important mechanism underlying the chemoresistance of ER (+) BC, advanced studies and validation are required.

• IMMUNE NETWORK
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• 제11권6호
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• pp.416-419
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• 2011

Dextran sodium sulfate (DSS) is a widely used chemical model for inflammatory bowel disease (IBD). It is thought that imbalances in the T helper (Th) cell subsets contribute to IBD. Recent studies suggest that the acute DSS-colitis model is polarized toward a Th1/Th17 profile based on RT-PCR analysis of colonic tissues. In the current study we determined whether colonic Th cells from DSS-colitis mice were skewed toward the Th17 profile. Mice were treated with 5% DSS for 7 days and colonic T cells isolated and examined for production of IFN-${\gamma}$ (Th1 cell), IL-4 (Th2 cell) and IL-17 (Th17 cell) by intracellular flow cytometry. We found that the percentage of colonic Th17 cells were similar to non-treated controls but the percentage of Th1 cells were elevated in DSS-colitis mice. These results suggest that in the acute DSS-colitis model the colonic Th cells exhibit a Th1 profile and not a Th17 profile.

• Journal of Microbiology and Biotechnology
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• 제28권1호
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• pp.65-76
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• 2018

Although there has been a steady increase in the prevalence of food allergies worldwide in recent decades, no effective therapeutic strategies have been developed. Modulation of the gut microbiota composition and/or function through probiotics has been highlighted as a promising target for protection against food allergies. In this study, we aimed to investigate the allergy-reducing effects of a probiotic mixture (P5: Lactococcus lactis KF140, Pediococcus pentosaceus KF159, Lactobacillus pentosus KF340, Lactobacillus paracasei 698, and Bacillus amyloliquefaciens 26N) in mice with ovalbumin (OVA)-induced food allergy. Administration of P5 significantly suppressed the oral OVA challenge-induced anaphylactic response and rectal temperature decline, and reduced diarrhea symptoms. Moreover, P5 also significantly inhibited the secretion of IgE, Th2 cytokines (interleukin (IL)-4, IL-5, IL-10, and IL-13), and Th17 cytokines (IL-17), which were increased in mice with OVA-induced food allergy, and induced generation of CD4+Foxp3+ regulatory T cells. These results revealed that P5 may have applications as a preventive agent against food allergy.

• Asian Pacific Journal of Cancer Prevention
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• 제17권11호
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• pp.4977-4982
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• 2016

Introduction: Elevated serum interleukin (IL) 6 has been reported in patients infected with the hepatitis C virus (HCV), but it remains debatable whether this influences the production of autoantibodies and the biochemical profile of HCV disease. Therefore, this current study was conducted to evaluate the relationship between IL-6 and circulating autoantibody levels in HCV positive patients. Methods: Levels of IL-6 in serum samples from 102 patients with HCV and 103 normal controls were determined by enzyme linked immunosorbent assay (ELISA). Autoantibodies were detected by immunofluorescence. Results: Levels of IL-6 were significantly higher (p=0.028) in patients infected with (HCV) compared with normal group. Autoantibodies were noted in in 43.1% of the patients; of these, 23.5% featured anti-nuclear antibodies (ANA+), 16.7% anti-smooth muscle antibodies (ASMA+), 7.8% anti-mitochondrial antibodies (AMA+), 17.6% anti-parietal cell antibodies (APCA+), 7.8% anti canalicular antibodies, and 2.9% anti reticulin antibodies (ARA+). No patients were found to be positive for anti-brush border antibodies (ABBA) or anti-ribosomal antibodies. (ARiA). No links with IL-6 levels were apparent. Conclusions: IL-6 levels are increased in patients infected with HCV disease and could influence the production of autoantibodies. However, this study did not provide evidence of a specific relationship between IL6 and circulating autoantibodies in such cases.

• IMMUNE NETWORK
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• 제21권6호
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• pp.43.1-43.14
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• 2021

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4⁺ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22⁺ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22⁺ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22⁺ ILC3, NKp44^- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP⁺ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22⁺ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22⁺ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

• BMB Reports
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• 제54권5호
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• pp.260-265
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• 2021

Dysregulation of inflammation induced by noninfectious stress conditions, such as nutrient deprivation, causes tissue damage and intestinal permeability, resulting in the development of inflammatory bowel diseases. We studied the effect of autophagy on cytokine secretion related to intestinal permeability under nutrient deprivation. Autophagy removes NLRP3 inflammasomes via ubiquitin-mediated degradation under starvation. When autophagy was inhibited, starvation-induced NLRP3 inflammasomes and their product, IL-1β, were significantly enhanced. A prolonged nutrient deprivation resulted in an increased epithelial mesenchymal transition (EMT), leading to intestinal permeability. Under nutrient deprivation, IL-17E/25, which is secreted by IL-1β, demolished the intestinal epithelial barrier. Our results suggest that an upregulation of autophagy maintains the intestinal barrier by suppressing the activation of NLRP3 inflammasomes and the release of their products, including pro-inflammatory cytokines IL-1β and IL-17E/25, under nutrient deprivation.

• 혜화의학회지
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• 제24권2호
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• pp.35-57
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• 2016

Objectives : The purpose of this study is to prove the effect and mechanism of Gamikyejakjimogawusul-tang(GKHA) herbal acupuncture on induced rheumatoid arthritis model of DBA/1 mice. Methods : We check effect of GKHA extract on the AST, ALT, Creatinine, BUN of serum and cell viability of GK extract in RAW 264.7 cells to test the stability of this study. In vitro, we measure total phenol contents, total flavonoid contents, DPPH free radical scavenging activity, ABTS cation radical scavenging activity of Gamikyejakjimogawusul-tang, effect of GK extract on ROS(Reactive Ooxygen Species) production to estimate a anti-oxidant capacity, and we also measure effect of GK extract on NO (Nitric Oxid), IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF production in RAW 264.7 cells to estimate a anti-inflammatory efficacy. In vivo, we compare a rheumatoid arthritis manifestation between control and experimental group and estimate a AI. Then we check effect of GKHA on the level of WBC, neutrophil, lympocyte, monocyte in the blood to see the effect of immune cells in blood. In addition we measure effect of GKHA on the level of hs-CRP, IgM, IgG, IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF in serum. We observe effects of GKHA on imaging of cartilage degeneration using micro CT-arthrography in paw hind. And we calculate effects of GKHA that reduced BV ratio, BS/BV ratio using 3D Micro-CT. Lastly we observe effects of GKHA histopathologic examination analysis. Results : 1. The toxicity on liver and kidney was disregardable and the cytotoxicity against RAW 264.7 cells was also disregardable. 1. Total phenol contents and total flavonoid contents in GK extract were in high level. 2. DPPH free radical scavenging activity and ABTS cation radical scavenging activity were increased according to concentration of GK extract 3. ROS production was significantly decreased in GK extract (at 10, $100{\mu}g/ml$). 4. NO, IL-6, TNF-${\alpha}$, MCP-1 production were significantly decreased in GK extract(at 10, $100{\mu}g/ml$). IL-17, GM-CSF production were significantly decreased in GK extract(at 1, 10, $100{\mu}g/ml$). IL-$1{\beta}$, IL-21 production were also decreased but there was no statistical significance. 5. 25x observation after H&E and M-T staining, infiltration of immune cells and subsidence of the cartilage and damage to the synovial cells were decreased. Conclusions : This study showed that GKHA extract had anti-oxidant capacity, anti-inflammatory efficacy. GKHA extract also had inhibiting effect on the process of rheumatoid arthritis and can protect joint and cartilage. So we expect that GKHA extract can be a meaningful treatment to rheumatoid arthritis patients.