The Th1 vs. Th2 balance is critical for the maintenance of immune homeostasis. Therefore, the genes that are selectively-regulated by the Th1 and Th2 cytokines are likely to play an important role in the Th1 and Th2 immune responses. In order to search for and identify the novel target genes that are differentially regulated by the Th1/Th2 cytokines, the human PBMC mRNAs differentially expressed upon the stimulation with IL-4 or IL-12, were screened by employing the differential display-polymerase chain reaction. Among a number of clones selected, DC21 was identified as a novel target gene that is regulated by IL-4 and IL-12. The DC21 gene expression was up-regulated either by IL-4 or IL-12, yet counter-regulated by co-treatment with IL-4 and IL-12. DC21 is a dendritic cell protein with an unknown function. The sequence analysis and conserved-domain search revealed that it has two AU-rich motifs in the 3'UTR, which is a target site for the regulation of mRNA stability by cytokines, and that it belongs to the N-acetyltransferase family. The induction of DC21 by IL-12 peaked around 8-12 h, and lasted until 24 h. LY294002 and SB203580 significantly suppressed the IL-12-induced DC21 gene expression, which implies that PI3K and p38/JNK are involved in the IL-12 signal transduction pathway that leads to the DC21 expression. Furthermore, tissue blot data indicated that DC21 is highly expressed in tissues with specialized-resident macrophages, such as the lung, liver, kidney, and placenta. Together, these data suggest a possible role for DC21 in the differentiation and maturation of dendritic cells regulated by IL-4 and IL-12.
Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.
CD4+ T helper (Th) cells play a crucial role in the modulation of innate and adaptive immune responses through the differentiation of Th precursor cells into several subsets, including Th1, Th2, Th17, and regulatory T (Treg) cells. Effector Th and Treg cells are distinguished by the production of signature cytokines and are important for eliminating intracellular and extracellular pathogens and maintaining immune homeostasis. Stimulation of naive Th cells by T cell receptor and specific cytokines activates master transcription factors and induces lineage specification during the differentiation of Th cells. The master transcription factors directly activate the transcription of signature cytokine genes and also undergo post-translational modifications to fine-tune cytokine production and maintain immune balance through cross-regulation with each other. This review highlights the post-translational modifications of master transcription factors that control the differentiation of effector Th and Treg cells and provides additional insights on the immune regulation mediated by protein argininemodifying enzymes in effector Th cells.
The general term flavonoids is often used to categorize a family of natural compounds that are highly abundant in all higher plants, and which in recent years have attracted scientific interest as therapeutics. Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. It is found in green vegetables such as spinach and kale, and has been demonstrated to exert anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. In this study, we attempt to determine whether lutein regulates inflammatory mediators in an ovalbumin (OVA)-induced murine asthma model. To address this, mice were sensitized and challenged with OVA, and then treated with lutein before the last OVA challenge. Administration of lutein significantly suppressed the OVA-induced airway hyper-responsiveness. It also resulted in a significant alleviation of the infiltration of inflammatory cells into the bronchoalveolar lavage. Additionally, lutein attenuated the increased expression of Th2 responses in OVA-challenged mice. These results demonstrate that lutein is a potent inhibitor that reduces Th2 immune responses. Furthermore, they show that the immunopharmacological function is mediated by a pathway that involves and is regulated by Th2 immune response.
The purposes of this study were to test the effect of balance training and environmental enrichment on motor performance after traumatic cerebellar injury in the rat. Traumatic cerebellar injury was induced by weight drop model and after operation they were housed in individual standard cages for 24 hours. Twenty two Sprague-Dawley rats were randomly assigned into control and experimental groups. The control group was housed in standard cage for 7 days. The experimental group I was housed in standard cage after balance training for 7 days. The experimental group II was housed in environmental enrichment cage after balance training for 7 days. Vestibular drop test and tilting plane test was examined at preoperation, on 1st day after operation and 7th day after operation to the rats. The results of this experiment were as follows: 1. In motor behavioral test, at preoperation and on 1 day after operation, the outcomes were not different among the groups. But on 7th day after operation, the outcomes of group I were better than that in control group, and group II were better than group I. These results suggest that behavioral motor outcome by simultaneously application of balance training and environmental enrichment in traumatic cerebellar injured rats were more improve than that by just balance training.
Phosphorylated dextran (P-Dex) is an acidic polysaccharide that functions as an immune adjuvant. P-Dex is known to regulate immune response by maintaining a balance between Th1 and Th2 cells in vitro, and thus may also be important in the control of allergic reactions. In the current study, we report the optimum conditions required for the efficient phosphorylation of dextran without toxicity. We found that when dextran was heated at 160${^{\circ}C}$ for 24 h in phosphate buffer (pH 5.0), the resulting P-Dex demonstrated the highest phosphorus content (6.8%). We also report that P-Dex enhances mitogenic activity in mouse splenocytes and induces expression of CD69 and CD86 on the surface of B cells and dendritic cells (DC) in vitro. Oral administration of P-Dex to ovalubmin (OVA)-immunized mice was found to reduce antigen-induced cell proliferation and suppress the expression of CD86 on Th2-inducing DC via exogenous OVA stimulation. P-Dex was also found to increase IL-10 expression in the splenocytes of treated mice. These findings suggest that oral administration of P-Dex increases immunological tolerance and improves the specificity of immunological response to specific antigens.
The objective of this study is to evaluate the effect of increasing instream flow at Gapcheon stream of Daejeon city by considering two virtual reservoirs upstream, respectively; Geum-gok reservoir and Koe-gok reservoir upstream, respectively. The paralleled and cascaded reservoir operations were performed including the existing Jang-an and Bang-dong reservoirs. The results are summarized as follows. Firstly, from the Bang-dong and Geum-gok cascaded reservoir's water balance analysis, instream flow of $6.83Mm^3$ was able to be supplied to downstream, and water supply indexes of Geum-gok reservoir were analyzed to have the rate of water supply divided by watershed area of 403.4 mm, the rate of water supply divided by rainfall of 33.0 %, the rate of water supply divided by inflow of 96.4 %, the rate of water supply divided by storage capacity of 81.9 %, and the rate of inflow divided by storage capacity of 112.3 %. Secondly, from the Jang-an and Geum-gok paralleled reservoir's water balance analysis, flow durations at Gapcheon station were analyzed to have Q95 (the 95th high flow) of $4.806m^3/s$, Q185 (the 185th high flow) of $2.217m^3/s$, Q275 (the 275th high flow) of $1.140m^3/s$, and Q355 (the 355th high flow) of $0.887m^3/s$. Thirdly, inflow to Koe-gok reservoir was simulated including the Jang-an and Bang-dong paralleled reservoir's water balance analysis, instream flow of $49.60Mm^3$ was able to be supplied from Koe-gok reservoir to downstream, and water supply indexes of Koe-gok reservoir were analyzed to have the rate of water supply divided by watershed area of 246.5 mm, the rate of water supply divided by rainfall of 19.4 %, the rate of water supply divided by inflow of 40.8 %, the rate of water supply divided by storage capacity of 412.1 %, and the rate of inflow divided by storage capacity of 1,189.8 %. Fourthly, daily streamflows at Gapcheon stream were simulated including outflows from Koe-gok reservoir, flow durations at Gapcheon station were analyzed to have Q95 (the 95th high flow) of $4.501m^3/s$, Q185 (the 185th high flow) of $2.277m^3/s$, Q275 (the 275th high flow) of $1.743m^3/s$, and Q355 (the 355th high flow) of $1.564m^3/s$. The conclusion appeared that the effect of increasing instream flow at Gapcheon stream from Koe-gok reservoir was more higher than that from Geum-gok reservoir.
The objective of this study was to determine the effect of exercise on a hemiparkinsonian rat model. Nigrostriatal dopamine cell lesions were produced by injecting 6-hydroxydopamine at the left medial forebrain bundle of rats. In this study, the rats were divided into the following 4 groups: the control group without any exercise, experimental group I with aqua-exercise (Exp I), experimental group II with balance exercise (Exp II) and experimental group III with complex exercise (aqua-exercise+balance exercise; (Exp III)). Exercises were applied to all the experimental groups after the operation. In order to observe the dopaminergic cell loss, we assessed the level of tyrosine hydroxylase (TH) expression in the midbrain of rats, and performed the apomorphine-induced rotation test at postoperative days (PDs) 7, 14, and 21. Experimental groups had significantly higher TH-immunoreactivity and behavioral performance than the control group. However, there was no difference in TH-immunoreactivity and behavioral performance across the experimental groups. These results suggest that the application of aqua-exercise and balance exercise could suppress dopaminergic cell loss in the substantia nigra of rat brains and could increase behavioral recovery in hemiparkinsonian rats.
Lee Tae Hyong;Kang Hee;Myung Eu Gene;Shim Bum Sang;Choi Seung Hoon;Kim Sung Hun;Ahn Kyoo Seok
Journal of Physiology & Pathology in Korean Medicine
/
v.18
no.2
/
pp.580-585
/
2004
BJYGC is often clinically used as a treatment of allergic rhinitis. This study was aimed to find out the effect BJYGC would have on the helper T cell, and how it can promote the subsets of helper T cells to regain their balance that they lost due to immunological diseases. Splenocytes were prepared from BALB/c mice was cultured without stimulation in the presence of BJYGC for 48 hr. The viability of CD4 T cells from Balb/c mouse were measured at various concentrations of BJYGC using the MTS assay. It was somewhat increased up to concentration of 400 ㎍/ml, but did not show any significant difference. Proliferation was measured using the MTS assay, CD4 Th cells were stimulated with anti-CD3/28 in the presence of BJYGC for 48 hr. As evidence for rapid T cell activation, CD25 expression by flow cytometry was evaluated at 10, 50, 100 and 200 ㎍/㎖ of BJYGC. Th cell differentiation experiments were performed to examine whether BJYGC can affect the Th polarization process. CD4 T cells were activated in culture under neutral, Th1-polarized or Th2-polarized conditions in the presence of BJYGC at 10, 100 and 200 ㎍/㎖. Cytokine production was measured by ELISA. This experiment proved that BJYGC could inhibit the secretion of both IL-4 and IFN-γ in neutral condition and polarized condition, too. Considering that BJYGC shows an excellent effect on treating allergies, the author can conclude that its pharmacological action may be associated with decreased IL-4 and, it may also regulate IFN-γ depending the host's need. Also, it was discovered that Th1 cell was pathologic in chronic inflammatory tissue specific diseases, such as insulin dependent diabetes mellitus, multiple sclerosis, RA, and uveitis. We are counting on the BJYGC to be able to control the tendency of Th1 cell predominancy in an immune reaction.
The recently released the $8^{th}$ edition of the American Joint Committee on Cancer (AJCC) Staging Manual introduces significant modifications from the prior $7^{th}$ edition. In this paper, the contents of the new changes in the decision of cancer of the head and neck is summarized except changes in staging of skin and thyroid cancer. In addition to the 8th edition, 1) Addition of extracapsular involvement in metastatic lymph nodes (N category) 2) Oral cancer T classification change, 3) Staging of the pharyngeal cancer was divided into 3 chapters: high-risk human papilloma virus (HR-HPV) associated oropharyngeal cancer (OPC), non HR-HPV associated OPC and hypopharynx cancer (HPC), and nasopharynx cancer (NPC) 4) Changes in T and N classification in NPC, 5) In the case of cancer of unknown primary, P16-positive case is defined as HR-HPV related OPC, and EBV-positive case is defined as NPC. The process that led to these changes highlights the need to collect high-fidelity cancer registry-level data that can be used to confirm prognostic observations identified in institutional data sets. Clinicians will continue to use the latest information for patient care, including scientific content of the 8th Edition Manual. All newly diagnosed cases through December $31^{st}$ 2017 should be staged with the 7th edition. The time extension will allow all partners to develop and update protocols and guidelines and for software vendors to develop, test, and deploy their products in time for the data collection and implementation of the 8th edition in 2018. The 8th edition strikes a balance between a personalized, complex system and a more general, simpler one that maintains the user-friendliness and worldwide acceptability of the traditional TNM staging paradigm.
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