• Title/Summary/Keyword: Th2 differentiation

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Chitinase 3-like-1, a novel regulator of Th1/CTL responses, as a therapeutic target for increasing anti-tumor immunity

  • Kim, Do-Hyun;Choi, Je-Min
    • BMB Reports
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    • v.51 no.5
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    • pp.207-208
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    • 2018
  • Chitinase-Like Proteins (CLPs) are an evolutionarily conserved protein which lose their enzymatic activity for degrading chitin macromolecules. Chitinase-3-like-1 (Chi3l1) is a type of CLP that is highly expressed in epithelial cells, macrophages, etc., and is known to have correlations with type 2 inflammation and cancer. Although the increased level of Chi3l1 in the blood was reported in various disease patients, the function of Chi3l1 in adaptive immunity has been totally unknown. Recently, we found that Chi3l1 is expressed in T cells and has a negative regulatory role in T-cell activation and proliferation. A genetic ablation study of Chi3l1 in T cells showed hyperresponsiveness to TcR stimulation, which increased proliferation and Th1 differentiation. A significant increase of $IFN{\gamma}$ signaling in Chi3l1-deficient T cells synergistically increased Th1 and CTL functions against melanoma cells in vitro and in vivo. In addition, targeted knockdown by Chi3l1 siRNA complexed with the cell-penetrating peptide dNP2, which showed decreased pulmonary melanoma metastasis with increased infiltration of Th1 and CTL in the lung. This study first suggests that Chi3l1 is a novel regulator of Th1/CTL responses and could be a target for treating cancer to increase tumor immunity.

AN ELECTRON MICROSCOPIC STUDIES OF RADIATION EFFECTS ON THE ENAMEL DEVELOPMENT OF THE RAT MOLAR (방사선조사가 백서구치법랑질발육에 미치는 영향에 관한 전자현미경적 연구)

  • Cho Hyo-Suck;You Dong-Soo
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.25 no.2
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    • pp.483-499
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    • 1995
  • Mandibular first molars of the rats were undertaken to observe the radiosensitivity of amelogenesis. Twenty four Sprague-Dawley rats received 396cGy radiation with the MK Cell irradiator using Cs-137, and twenty four rats served as control. They were devided into two groups; Group 1 which received radiation at the 14th day after gestation and group 2 which received radiation at the 19th day after gestation. Light Microscopy and Transmitted Electron Microscopy investigation was undertaken in the group 1 at the 15th, 18th, 20th, 22nd(2 days after birth), and 25th day(5 days after birth) after gestation, and in the group 2 at the 21th(birth day), 22nd(2 days after birth), and 25th(5 days after birth) day after gestation. The following histopathologic findings were obtained. 1. Compared with control group, experimental group showed a delayed formation of enamel and dentin due to slow rate of differentiation of undifferentiated mesenchymal cells. 2. In the experimental groups, the arrangement of the inner enamel epithelium was irregular and there were many vacuoles in the cytoplasm. There were dilated rER and mitochondria, increase of the intercellular space, and loss of the cellular polarity. 3. In the group 1, early enamel without Tomes' process, and early organic matrix was observed at the 25th day after gestation. 4. In the group 2, histopathologic changes were similar to those of the group 1, but the degree of changes was more severe than that of the group 1.

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Identification of DC21 as a Novel Target Gene Counter-regulated by IL-12 and IL-4

  • Kong, Kyoung-Ah;Jang, Ji-Young;Lee, Choong-Eun
    • BMB Reports
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    • v.35 no.6
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    • pp.623-628
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    • 2002
  • 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.

Effects of Interpersonal Relationship, Self Differentiation on College Adjustment in Nursing Students (간호대학생의 대인관계능력, 자아분화가 대학생활적응에 미치는 영향)

  • Lim, Mi-Hye
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.9
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    • pp.225-233
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    • 2018
  • The purpose of this study was to investigate the level of interpersonal relationship, self differentiation and adjustment to college life as well as to identify the factors influencing the adjustment to college life in nursing students. The study was conducted on 185 nursing students in D and S Province and from November 15th to December 5th 2016. The data was analyzed using t-test, one-way ANOVA, Pearson's correlation and Multiple regression. The mean score of the adjustment to college life was $3.30({\pm}0.49)$ and the interpersonal relationship was $3.73({\pm}0.41)$ and self differentiation was $3.07({\pm}0.32)$. There were positive correlations between adjustment to college life and interpersonal relationship(r=.614, p<.001) and self differentiation((r=.264, p<.001). Significant factors influencing adjustment to college life were interpersonal relationship, self differentiation which explained 39% of adjustment to college life. Based on these findings, programs that develop interpersonal relationship and self differentiation are necessary for college nursing students in order to promote college adjustment.

The Effects of Hataedock on 2,4-dinitrofluorobenzene Induced Atopic Dermatitis Like Skin Lesion in NC/Nga Mice (하태독법 중 황련감초법이 DNFB로 유발된 NC/Nga 생쥐의 아토피 피부염에 미치는 영향)

  • Cha, Ho Yeol;Ahn, Sang Hyun;Jeong, A Ram;Cheon, Jin Hong;Park, Sun Young;Kim, Ki Bong
    • The Journal of Pediatrics of Korean Medicine
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    • v.29 no.4
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    • pp.97-107
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    • 2015
  • Objectives Hataedock is the treatment that dispels toxic heat and meconium gathered at the fetus for the new born baby by orally administered herbal extracts. The purpose of this study was to evaluate whether Hataedock alleviate inflammatory skin damages in AD-induced NC/Nga mice through regulating of skin barrier maintain and Th2 differentiation. Methods We established an AD model in the 3-week-old NC/Nga mice through the repeated application of DNFB (dinitrochlorobenzene) on days 28, 35, 42 after Hataedock treatment which was orally administered. We identified the changes of skin barrier and Th2 differentiation through the histological and immunohistochemical changes of protein kinase C (PKC), interleukin (IL)-4, degranulated mast cell, Substance P and MMP-9. Results Our results suggested that Hataedock treatment significantly down-regulated levels of PKC by 82% (p < 0.001), as well as IL-4 by 56% (p < 0.001). Hataedock also suppressed mast cell infiltration, ear edema formation. and Substance P in the tissue of NC/Nga mice were decreased by 57% (p < 0.001), and MMP-9 by 55% (p < 0.001). Conclusions These results suggest that Hataedock alleviates AD through the down-regulation of PKC and Th2 cytokines, which are involved in the initial steps of AD development. Hataedock have potential application for the treatment of AD.

IMMUNOHISTOCHEMICAL STUDY FOR THE EXPRESSION OF BMP-2/4 ON THE HEALING PROCESS IN THE MANDIBULAR BONE DEFECT OF RAT (백서의 하악골 결손부 치유시 골형성단백질 2/4의 발현에 관한 연구)

  • Choi, Jae-Yong;Lee, Sang-Chull
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.26 no.4
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    • pp.325-336
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    • 2000
  • Bone morphogenetic protein-2/4 are members of Transforming Growth Factor-$\beta$(TGF-$\beta$) superfamily and they may induce formation of cartilage and bone in vivo. This study was performed to investigate the cellular target and period of action of BMP-2/4 and understanding of actions of BMP-2/4 at cellular level. The appearance of BMP-2/4 during healing of mandibular and periodontal defect in rat was evaluated immunohistochemically. 40 Sprague-Dawley strain white male rats, each weighing about 300gm were used. Bony defect was performed in the mandible and they were sacrificed at the day of 3rd, 10th, 20th, 30th after operation. The specimens were harvested and examined histologically and immunohistochemically by localization of anti-BMP-2/4. The results were as follows: 1. Woven bone was observed at 10th day and perfect healing of defect with compact bone and periodontal ligment space at 30th day. 2. Osteoprogenitor cells, osteoblastic cells and periosteum were positive reaction to immunohistochemical stain at 10th day. 3. Cells of bone marrow space and surface cells of osteocytes and cementoblasts were positive reaction to immunohistochemical stain at 20th day. 4. Newly formed osteocytes and cementocytes were positive reaction to immunohistochemical stain at 30th day. From the above findings, we could conclude that BMP-2/4 acted significant roles as factors of induction, proliferation and differentiation during bone healing process.

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EFFECT OF ENAMEL MATRIX DERIVATIVE (EMD, $EMDOGAIN^{(R)}$) ON THE DIFFERENTIATION OF CULTURED HUMAN PERIODONTAL LIGAMENT CELLS AND MESENCHYMAL STEM CELLS (배양된 사람 치주인대세포와 골수유래간엽줄기세포의 분화에 미치는 법랑기질유도체 (Enamel Matrix Derivative, EMD)의 영향)

  • Park, Sang-Gyu;Jue, Seong-Suk;Kwon, Yong-Dae;Choi, Byung-Joon;Kim, Young-Ran;Lee, Baek-Soo
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.31 no.4
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    • pp.281-286
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    • 2009
  • Introduction: Enamel matrix derivative (EMD) is a protein which is secreted by Hertwig root sheath and plays a major role in the formation of cementum and attachment of peridontium. Several studies have shown that EMD promoted the proliferation and differentiation of preosteoblasts, osteoblasts and periodontal ligament cells in vitro: however, reports showing the inhibition of osteogenic differentiation by EMD also existed. This study was designed to simultaneously evaluate the effect of EMD on the two cell lines (human mesenchymal stem cells: hMSC, human periodontal ligament derived fibroblasts: hPDLCs) by means of quantitative analysis of some bone related matrices (Alkaline phosphatase : ALP, osteopontin ; OPN, osteocalcin ; OC). Materials and Methods: hMSCs and hPDLCs were expanded and cells in the 4${\sim}$6 passages were adopted to use. hMSc and hPDLCs were cultured during 1,2,7, and 14 days with 0, 50 and 100 ${\mu}g/ml$ of EMD, respectively. ALP activity was assessed by SensoLyte ALP kit and expressed as values of the relative optical density. Among the matrix proteins of the bony tissue, OC and OPN were assessed and quantification of these proteins was evaluated by means of human OC immunoassay kit and human OPN assay kit, respectively. Results: ALP activity maintained without EMD at $1,2^{nd}$ day. The activity increased at $7^{th}$ day but decreased at $14^{th}$ day. EMD increased the activity at $14^{th}$ day in the hPDLCs culture. In the hMSCs, rapid decrease was noted in $7^{th}$ and $14^{th}$ days without regard to EMD concentrations. Regarding the OPN synthesis in hPDLCs, marked decrease of OPN was noted after EMD application. Gradual decrease tendency of OPN was shown over time. In hMSCs, marked decrease of OPN was also noted after EMD application. Overall concentration of OPN was relatively consistent over time than that in hPDLCs. Regarding the OC synthesis, in both of hPDLCs and hMSCs, inhibition of OC formation was noted after EMD application in the early stages but EMD exerted minimal effect at the later stages. Conclusion: In this experimental condition, EMD seemed to play an inhibitory role during the differentiation of hMSCs and hPDLCs in the context of OC and OPN formation. In the periodontium, there are many kinds of cells contributing to the regeneration of oral tissue. EMD enhanced ALP activity in hPDLCs rather than in hMSCs and this may imply that EMD has a positive effect on the differentiation of cementoblasts compared with the effect on hMSCs. The result of our research was consistent with recent studies in which the authors showed the inhibitory effect of EMD in terms of the differentiation of mineral colony forming cells in vitro. This in vitro study may not stand for all the charateristics of EMD; thus, further studies involving many other bone matrices and cellular attachment will be necessary.

Hwangnyeonhaedok-tang Extracts Ameliorates Atopic Dermatitis via Epidermal Lipid Barrier Regeneration in NC/Nga Mouse (황련해독탕의 피부지방장벽개선을 통한 Th2 분화조절이 아토피피부염 완화에 미치는 효과)

  • Son, Seong Han;Ahn, Sang Hyun;Park, Sun-Young;Kim, Kibong
    • The Journal of Pediatrics of Korean Medicine
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    • v.32 no.3
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    • pp.90-99
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    • 2018
  • Objectives Hwangnyeonhaedok-tang is a Korean herbal medical treatment that removes toxic heat, fever and inflammation. The purpose of this study was to investigate the effect of Hwangnyeonhaedok-tang treatment on the relief of atopic dermatitis (AD) through regeneration of skin lipid barrier. Methods Male NC/Nga mice (20 g, 6 week age) were used. Each 10 mice were allocated to the control group (Ctrl), the AD-induced with no treatment group (AE), and the group which induced AD after administering Hwangnyeonhaedok-tang extract (HT). To induce AD-like skin lesions, sodium dodecyl sulfate (SDS) (Sigma-Aldrich, USA) was rubbed on the back of each mouse to remove the lipid lamella of the stratum corneum, and Dermatophagoides (D.) farinae crude extract was applied. HT group was orally administered Hwangnyeonhaedok-tang after induction of AD. IL-4 IL-13, $p-I{\kappa}B$, iNOS, Sudan Black B (SB), loricrin, and filaggrin were observed to confirm the effect. Results In HT group, AD skin score was decreased by 46%. The cytokine IL-4 and IL-13, which can identify Th2 differentiation, was reduced by 73% and 58% each. Anti-inflammatory effects were observed in $p-I{\kappa}B$ and iNOS by 69% and 54%, respectively. Finally, SB showed that the regeneration of the lipid layer and the increase of the regeneration power of loricrin and filaggrin were increased by 437% and 464%, respectively. Conclusions From the study result, we observed that Hwangnyeonhaedok-tang treatment alleviates AD by decreasing skin score, reducing Th2 differentiation, inducing anti-inflammatory, and increasing skin lipid barrier regeneration. Thus, Hwangnyeonhaedok-tang treatment would be considered as an effective AD relieving treatment.

Expression of Gonadotropin-Releasing Hormone Gene in Mouse Fetal Ovary during Gonad Differentiation (생쥐의 생식소 분화과정중 난소내 Gonadotropin-Releasing Hormone 유전자의 발현)

  • 윤성희
    • Development and Reproduction
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    • v.1 no.2
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    • pp.189-202
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    • 1997
  • The hypothalamic peptide GnRH plays a central role in the regulation of the mammalian reproductive axis. Recent studies suggested that GnRH stimulates or inhibits the ovarian steroidogenesis and gametogenesis directly. Our previous report indicated that GnRH gene is expressed in adult rat ovary as well as in hypothalamus and that the expressed GnRH may induce the follicular atresia and apoptosis of ovarian granulosa cells in rat. Therfore, we studied whether GnRH gene is expressed in the mouse fetal ovary, when the germ cells are degenerating by apoptosis during gonad diffeerentiation. Mouse fetal gonads were obtained on the 12, 15,18 and 20th day of gestation from the mother mice superovulated (10 IU PMSG and 10 IU hCG) and mated. The morphological changes of fetal ovaries were examined histochemically by hematoxylin-eosin staining. The fetal sex was confirmed by PCR methods for sexing. RT-PCR methods were used to examine the expression of GnRH gene and the sex steroid hormones were determined by conventional radioimmunoassays. The levels of estradiol (E) and progesterone (P) were increaseduntil 18th day of gestation and then E was decreased just before parturition. The morphological changes of fetal gonadal tissue sections showed the ovarian development and coincided with the result of PCR analysis for sexing using ovary- or testis- specific oligonucleotide primers. Immunoreactive GnRH in placenta was decreased gradually until the end of gestation but fetal brain and ovarian GnRH were increased. The level of GnRH gene expression was increased during fetal ovarian development from 12 till 18th day and decreased suddenly on 20th day just before birth. From these results, it is suggested that ovarian GnRh may play a regulatory role on the germ cell differentiation of fetal ovary.

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Common and differential effects of docosahexaenoic acid and eicosapentaenoic acid on helper T-cell responses and associated pathways

  • Lee, Jaeho;Choi, Yu Ri;Kim, Miso;Park, Jung Mi;Kang, Moonjong;Oh, Jaewon;Lee, Chan Joo;Park, Sungha;Kang, Seok-Min;Manabe, Ichiro;Ann, Soo-jin;Lee, Sang-Hak
    • BMB Reports
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    • v.54 no.5
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    • pp.278-283
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    • 2021
  • Our understanding of the differential effects between specific omega-3 fatty acids is incomplete. Here, we aimed to evaluate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on T-helper type 1 (Th1) cell responses and identify the pathways associated with these responses. Naïve CD4+ T cells were co-cultured with bone marrow-derived dendritic cells (DCs) in the presence or absence of palmitate (PA), DHA, or EPA. DHA or EPA treatment lowered the number of differentiated IFN-γ-positive cells and inhibited the secretion of IFN-γ, whereas only DHA increased IL-2 and reduced TNF-α secretion. There was reduced expression of MHC II on DCs after DHA or EPA treatment. In the DC-independent model, DHA and EPA reduced Th1 cell differentiation and lowered the cell number. DHA and EPA markedly inhibited IFN-γ secretion, while only EPA reduced TNF-α secretion. Microarray analysis identified pathways involved in inflammation, immunity, metabolism, and cell proliferation. Moreover, DHA and EPA inhibited Th1 cells through the regulation of diverse pathways and genes, including Igf1 and Cpt1a. Our results showed that DHA and EPA had largely comparable inhibitory effects on Th1 cell differentiation. However, each of the fatty acids also had distinct effects on specific cytokine secretion, particularly according to the presence of DCs.