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진미림,윤주한 대한면역학회 2018 Immune Network Vol.18 No.6
Atopic dermatitis (AD) is the most common pruritic inflammatory skin disease characterized by thickening of epidermis and dermis as well as by the infiltration of multiple pathogenic polarized T lymphocytes, including Th2, Th17, and Th22 cells. Significant progress has been made to develop targeted therapeutics for treating AD, e.g., Food and Drug Administration-approved dupilumab, an antibody for dual targeting of IL-4 and IL-13 signaling pathways. Additionally, a growing body of published evidence and a promising result from the early stage of the clinical trial with ILV-094, an anti-IL-22 antibody, strongly support the notion that IL-22 is a potential therapeutic target for treating AD. Moreover, we also experimentally proved that IL-22 contributes to the pathophysiology of AD by employing a murine model of AD induced by epicutaneous sensitization. Here, we review recent preclinical and clinical findings that have advanced our understanding of the roles of IL-22 and Th22 cells in skin inflammation. We conclude that blockade of IL-22 signaling may be a promising therapeutic approach for the treatment of AD.
진미림,Soo Jeong Yoon,Myoung Yun Pyo 한국응용생명화학회 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.6
Fisetin, a flavonol, has been known as an anti-allergic agent having inhibitory effects on T helper 2 cytokine gene expression in inflammatory immune cells. However, its molecular mechanisms for suppressive effects of fisetin on interleukin (IL)-4 and IL-13 in activated mast cells and basophils have been incompletely understood. In this study we found that fisetin at the concentrations having no effect on cell viability significantly inhibited the phorbol 12-myristate 13-acetate and ionomycin induced production of IL-4 and IL-13 in bone marrow-derived mast cells and RBL-2H3 basophilic cells. The levels of mRNA were dramatically decreased by fisetin, indicating the suppression might be regulated at the transcriptional levels. Transient transfection experiments using luciferase reporter plasmids expressing IL-4 or IL-13 promoter revealed that fisetin inhibited the activation of the promoters in a dose-dependent manner. Western blot analysis of the nuclear expression of various transcription factors involved in the promoter activation indicated that suppressions of c-Fos and CCAAT/enhancer-binding protein alpha were prominent together with significant downregulations of nuclear factor of activated T cell (NF-AT) and NF-κB. Furthermore, nuclear expression of GATA-1 and GATA-2, and the mRNA expression were significantly down regulated by fisetin, whereas cyclosporine A had no significant effects on GATA transcription factors. Taken together, fisetin has suppressive effects on IL-4 and IL-13 gene expressions through the regulation of selective transcription factors.
Unique roles of tryptophanyl-tRNA synthetase in immune control and its therapeutic implications
진미림 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
Tryptophanyl tRNA synthetase (WRS) is an essential enzyme as it catalyzes the ligation of tryptophan to its cognate tRNA during translation. Interestingly, mammalian WRS has evolved to acquire domains or motifs for novel functions beyond protein synthesis; WRS can also further expand its functions via alternative splicing and proteolytic cleavage. WRS is localized not only to the nucleus but also to the extracellular space, playing a key role in innate immunity, angiogenesis, and IFN-γ signaling. In addition, the expression of WRS varies significantly in different tissues and pathological states, implying that it plays unique roles in physiological homeostasis and immune defense. This review addresses the current knowledge regarding the evolution, structural features, and context-dependent functions of WRS, particularly focusing on its roles in immune regulation.
잣버섯으로부터 분리한 성분의 분석 및 Protein kinase C를 경유하는 NF-kB 활성화 작용
진미림,정규선 숙명여자대학교 약학연구소 1998 약학논문집-숙명여자대학교 Vol.15 No.-
In the previous study we reported the isolated compounds from Lentinus lepideus as biological response modifiers, especially B cell mitogen. For the characterization of the compounds we performed anthrone test, Lowry-Foline test, hexosamine test, gas liquid chromatography and amino acid analysis. The results showed the acidic polysaccharide fraction, named lepidan, consists of protein bound polysaccharide which has galactose, xylose and mannose as monosaccharides. As one apprach to understanding the molecular mechanisms of this action, we investigated effects of the compound on cellular transcription factors which are known to control the proliferation of immune cells. Using transient transfection we found that lepidan significantly activated NF-kB in 70Z/3 pre B cell line, but not AP-1. Also activation of NF-kB by lepidan blocked by the protein kinase inhibitor H7. It suggested that the actions of lepidan on NF-kB was activated through the PKC pathway.
진미림,박선영,박보경,최정준,윤수정,양미희,표명윤 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.2
It is known that the intake of omega-3 fatty acids, such as eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), is beneficial for preventing and/or treating allergic diseases. The pathogenesis of allergic diseases is associated with overactivation of Th2-skewed immunity. Basophils generate large amounts of Th2 cytokines such as interleukin (IL)-4 and IL-13, which are critically involved in allergic inflammation. We investigated how EPA and DHA affect Th2 cytokine expression in phorbol 12-myristate 13-acetate- and ionomycin (PI)-activated RBL-2H3 basophilic leukemia cells. EPA and DHA induced a dramatic decrease in the production of IL-4 and IL-13 and their transcription in a dose-dependent manner. Luciferase assays of RBL-2H3 cells stably expressing Il4 and Il13 promoter–reporter plasmids demonstrated a significant suppression of PI-induced promoter activation. Analysis of certain transcription factors revealed that nuclear expression of c-Fos and the mRNA expression were suppressed by EPA and DHA. Furthermore, they significantly inhibited the nuclear expression and translocation of nuclear factor of activated T cells (NF-AT)1. In contrast, the expression levels of nuclear factor kappa-B (NF-jB), GATA-binding proteins (GATAs), and CCAAT/enhancer binding protein alpha (C/EBPa) were not significantly affected by EPA and DHA. Phosphorylation of extracellular signal-related kinase was inhibited by EPA and DHA, and phosphorylation of p38 mitogen-activated protein kinase was decreased by DHA, but not by EPA. Taken together, our data suggest that EPA and DHA may suppress Th2-skewed allergic immune responses by inhibiting the expression of basophilic IL-4 and IL-13.
잣버섯 균사체로부터 분리한 단백다당체의 암종에 따른 선별적 항암작용
진미림(Mi Rim Jin),정규선(Kyu Sun Jung),김병각(Byong Kak Kim) 대한약학회 1998 약학회지 Vol.42 No.5
Many antitumor and immune modulating components have been isolated from fungal extracts. In this study, the authors isolated the proteoglycans from cultured mycelia of Lentinus lepideus, including especially the acidic polysaccharide fraction, named lepidan. It was obtained by extraction with hot water followed by purification using DEAE cellulose anion exchange. To elucidate antitumor effects against different type of tumor, the proteoglycans were tested on sarcoma 180, C3H MCA clone 16 and P388 leukemia in vivo. Lepidan showed 58.3% of tumor inhibition against solid form of sarcoma 180 and 58.6% against MCA clone 16. But lepidan did not affect life span of mice against P388 leukemia. Also when Lepidan was applicated to MTT assay, it did not show any direct cytotoxicity against various tumor cells in vitro.