아황산가스가 흰쥐 허파조직내 Laminin 활서에 미치는 영향에 대한 면역조직학적 연구

배성만,정호삼,서윤경,백두진,김원규,윤지희 한양대학교 의과대학 2000 한양의대 학술지 Vol.20 No.2

Sulfur dioxide (SO_2), a kind of air pollutant, causes harmful damage to human body. In particular, inhalation of sulfoxide dioxide has been demonstrated to result in the injury to the upper respiratory duct. However, mechanisms by which SO_2 affects these tissues remain to be clarified. In the present study, to investigate the mechanism of SO_2 effects, the influence of SO_2 exposure was examined in terms of the injury of lung and the expression pattern of laminin in the basal lamina. The basal lamina is an important tissue for the regulation of internal respiration by composing of air-blood barrier. Sprague-Dawley rats repetitively exposed to a mixture of O_2 gas and SO_2 gas (250 ppm) for 30 minutes a day were sacrificed to observe the distribution of laminin in the alveolar septum as well as the morphological alteration of alveoli using immunohistological methods. The resutls we observed were as follows: 1. Alveoli from SO_2-exposed rats (for 5 days) were strongly stained with anti-laminin antibody, suggesting laminin expressed at the high level, at week 1 to 3 upon exposure to SO_2 2. At week 1 to 3 after exposure of rats to SO_2, alveolar septa were collapsed, leading to the reduction of alveolar volume along with morphological changes to irregular shapes. 3. At week 4 to 6 after exposure of rats to SO_2, alveoli were weakly stained with anti-laminin antibody, suggesting laminin expression was decreased during this period. 4. Rats sacrificed at week 7 upon exposure to SO_2 exhibited the expansion of new alveoli and the expression of laminin was partially recovered up to the intermediate level. Taken together, these results demonstrate that the expression of laminin was enhanced in the early phase, followed by downregulation in the late phase. Moreover, lung injury and resolution were correlated with the level of laminin. Thus, these results suggest that SO_2 suppresses the expression of laminin, which may be associated with the neo-generation of lung tissue.

Retinoic Acid가 흰쥐 태자 혀조직의 분화와 Laminin 합성에 미치는 영향에 대한 연구

김혜주,정호삼,서윤경,백두진,김원규,윤지희,이방헌 대한췌담도연구회 2000 대한췌담도연구회지 Vol.5 No.4

Mouse models of systemic lupus erythematosus

Jeehee Youn(윤지희) 한국실험동물학회 2022 한국실험동물학회 학술발표대회 논문집 Vol.2022 No.1

The Niche of Follicular Helper T Cells in Systemic Autoimmune Diseases

Jang, Eunkyeong,Youn, Jeehee Hanyang University College of Medicine (KAMJE) 2013 Hanyang medical reviews Vol.33 No.1

Rheumatoid Fibroblast-like Synoviocytes Downregulate Foxp3 Expression by Regulatory T Cells Via GITRL/GITR Interaction

Kim, Sung Hoon,Youn, Jeehee The Korean Association of Immunobiologists 2012 Immune Network Vol.12 No.5

Fibroblast-like synoviocytes (FLS) colocalize with leukocyte infiltrates in rheumatoid synovia. Proinflammatory leukocytes are known to amplify inflammation by signaling to FLS, but crosstalk between FLS and regulatory T cells (Tregs) remains uncharacterized. To address this possibility, we cocultured FLS lines derived from arthritic mice with Tregs. FLS that expressed the ligand for glucocorticoid-induced TNF receptor family-related gene (GITR) decreased expression of Foxp3 and GITR in Tregs in a contact-dependent manner. This effect was abolished by blocking antibody to GITR. On the other hand, the Tregs caused the FLS to increase IL-6 production. These results demonstrate that inflamed FLS license Tregs to downregulate Foxp3 expression via the GITRL/GITR interaction while the Tregs induce the FLS to increase their production of IL-6. Our findings suggest that the interaction between FLS and Tregs dampens the anti-inflammatory activity of Tregs and amplifies the proinflammatory activity of FLS, thereby exacerbating inflammatory arthritis.

IL-21 ensures TGF-β1-induced IgA isotype expression in mouse Peyer's patches

Seo, Goo-Young,Youn, Jeehee,Kim, Pyeung-Hyeun Wiley (John WileySons) 2009 Journal of Leukocyte Biology Vol.85 No.5

<P>It is well established that TGF-beta1 induces IgA and IgG2b class-switching recombination in murine B cells. In the present study, we assessed the activity of IL-21 along with TGF-beta1 in Ig synthesis by murine spleen B cells. IL-21 showed antiproliferative activity on LPS-activated splenic B cells, comparable with that of TGF-beta1. IL-21 alone had little effect on IgA secretion and decreased other isotypes. Likewise, IL-21 also did not alter the TGF-beta1-induced IgA synthesis and concurrently diminished the syntheses of IgM and IgG2a, which were repressed by TGF-beta1. Unexpectedly, IL-21 inhibited the TGF-beta1-induced IgG2b production. This IL-21 effect was examined using B cells from IL-21R knockout mice, where the IgA production profile was paralleled by that seen in wild-type B cells. However, the inhibitory effect of IL-21 on TGF-beta1-induced IgG2b synthesis was not seen in the IL-21R(-/-) mouse, suggesting that IL-21 causes TGF-beta1-stimulated B cells to decrease IgG2b synthesis. Expression patterns of Ig germ-line alpha(GL alpha)/GL gamma 2b transcripts under the influence of TGF-beta1 and IL-21 were paralleled by IgA/IgG2b secretion. This was also observed in the activities of GL(alpha) and GL(gamma 2b) promoters. These results indicate that IL-21 decreases IgG2b secretion mainly through inhibition of GL(gamma 2b) transcription and is ultimately associated with selective IgA secretion induced by TGF-beta1. Our results showed that IL-21 was expressed in greater magnitude in Peyer's patches (PP) than in spleen. These results suggest that IL-21 has an important effect on selective IgA(+) B cell commitment in PP.</P>

Arabidopsis ACC Oxidase 1 Coordinated by Multiple Signals Mediates Ethylene Biosynthesis and Is Involved in Root Development

Park, Chan Ho,Roh, Jeehee,Youn, Ji-Hyun,Son, Seung-Hyun,Park, Ji Hye,Kim, Soon Young,Kim, Tae-Wuk,Kim, Seong-Ki Korean Society for Molecular and Cellular Biology 2018 Molecules and cells Vol.41 No.10

Ethylene regulates numerous aspects of plant growth and development. Multiple external and internal factors coordinate ethylene production in plant tissues. Transcriptional and post-translational regulations of ACC synthases (ACSs), which are key enzymes mediating a rate-limiting step in ethylene biosynthesis have been well characterized. However, the regulation and physiological roles of ACC oxidases (ACOs) that catalyze the final step of ethylene biosynthesis are largely unknown in Arabidopsis. Here, we show that Arabidopsis ACO1 exhibits a tissue-specific expression pattern that is regulated by multiple signals, and plays roles in the lateral root development in Arabidopsis. Histochemical analysis of the ACO1 promoter indicated that ACO1 expression was largely modulated by light and plant hormones in a tissue-specific manner. We demonstrated that point mutations in two E-box motifs on the ACO1 promoter reduce the light-regulated expression patterns of ACO1. The aco1-1 mutant showed reduced ethylene production in root tips compared to wild-type. In addition, aco1-1 displayed altered lateral root formation. Our results suggest that Arabidopsis ACO1 integrates various signals into the ethylene biosynthesis that is required for ACO1's intrinsic roles in root physiology.

Dietary Vitamin E and Quercetin Modulate Inflammatory Responses of Collagen-Induced Arthritis in Mice

Eun-Jin Choi,배상철,Rina Yu,Jeehee Youn,성미경 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.4

Rheumatoid arthritis (RA) is characterized by chronic inflammation of the synovial joints. This study investigated whether or not a diet deficient in vitamin E is a possible risk factor in the development of RA and evaluated the efficacy of antioxidant supplementation. Male DBA/1J mice were maintained on either a control diet (C) or a vitamin E-depleted (−VE) diet for 4 weeks before arthritis induction. The mice in the control group were subdivided into the control group (C/C), the 0.05% α-tocopherol-supplemented group (C/+VE), and the 0.5% quercetin-supplemented group (C/+Q). The vitamin E-depleted group was subdivided into the −VE group (−VE/−VE), the 0.05% α-tocopherol-supplemented group (−VE/+VE), and the 0.5% quercetin-supplemented group (−VE/+Q) (in total, six groups, 27 mice per group). The mice were maintained on the experimental diets for 9 weeks. Study results indicate that the −VE/−VE group showed higher joint tissue tumor necrosis factor-α and interleukin-1β mRNA expressions, whereas α-tocopherol or quercetin supplementation reduced tissue cytokine mRNA levels to values comparable to those of the C/C group. The mice fed the −VE/−VE diet exhibited higher levels of circulating macrophage chemoattractant protein 1, nitric oxide, and prostaglandin E2 compared to those in other groups. Supplementation with α-tocopherol or quercetin in mice fed −VE diet decreased these markers similar to those of the mice in the C/C group. No supplementation effect was observed, however, in the mice fed with the control diet prior to RA induction. These results suggest that dietary deficiency of vitamin E increases inflammatory responses and that antioxidants successfully suppress the inflammatory responses. However, significant clinical improvement may require longer observation.

Early Growth Response-1 Plays a Non-redundant Role in the Differentiation of B Cells into Plasma Cells

Oh, Yeon-Kyung,Jang, Eunkyeong,Paik, Doo-Jin,Youn, Jeehee The Korean Association of Immunobiologists 2015 Immune Network Vol.15 No.3

Early growth response (Egr)-1 is a $Cys_2-His_2-type$ zincfinger transcription factor. It has been shown to induce survival and proliferation of immature and mature B cells, respectively, but its role in the differentiation of B cells into plasma cells remains unclear. To examine the effects of Egr-1 deficiency on the activation of B cells, naive B cells from $Egr1^{-/-}$mice and their wild-type (WT) littermates were activated to proliferate and differentiate, and then assayed by FACS. Proportions of cells undergoing proliferation and apoptosis did not differ between $Egr1^{-/-}$ and WT mice. However, $Egr1^{-/-}$ B cells gave rise to fewer plasma cells than WT B cells. Consistently, $Egr1^{-/-}$ mice produced significantly lower titer of antigen-specific IgG than their WT littermates upon immunization. Our results demonstrate that Egr-1 participates in the differentiation program of B cells into plasma cells, while it is dispensable for the proliferation and survival of mature B cells.

Insights into the Role of Follicular Helper T Cells in Autoimmunity

Park, Hong-Jai,Kim, Do-Hyun,Lim, Sang-Ho,Kim, Won-Ju,Youn, Jeehee,Choi, Youn-Soo,Choi, Je-Min The Korean Association of Immunobiologists 2014 Immune Network Vol.14 No.1

Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.