Ji Hyeon Ju

Bio: Ji Hyeon Ju is an academic researcher from Catholic University of Korea. The author has contributed to research in topics: Arthritis & Induced pluripotent stem cell. The author has an hindex of 40, co-authored 212 publications receiving 5172 citations. Previous affiliations of Ji Hyeon Ju include Dongguk University & St Mary's Hospital.

STAT3 and NF-κB Signal Pathway Is Required for IL-23-Mediated IL-17 Production in Spontaneous Arthritis Animal Model IL-1 Receptor Antagonist-Deficient Mice

Abstract: IL-23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 has proinflammatory activity, inducing IL-17 secretion from activated CD4+ T cells and stimulating the proliferation of memory CD4+ T cells. We investigated the pathogenic role of IL-23 in CD4+ T cells in mice lacking the IL-1R antagonist (IL-1Ra−/−), an animal model of spontaneous arthritis. IL-23 was strongly expressed in the inflamed joints of IL-1Ra−/− mice. Recombinant adenovirus expressing mouse IL-23 (rAd/mIL-23) significantly accelerated this joint inflammation and joint destruction. IL-1β further increased the production of IL-23, which induced IL-17 production and OX40 expression in splenic CD4+ T cells of IL-1Ra−/− mice. Blocking IL-23 with anti-p19 Ab abolished the IL-17 production induced by IL-1 in splenocyte cultures. The process of IL-23-induced IL-17 production in CD4+ T cells was mediated via the activation of Jak2, PI3K/Akt, STAT3, and NF-κB, whereas p38 MAPK and AP-1 did not participate in the process. Our data suggest that IL-23 is a link between IL-1 and IL-17. IL-23 seems to be a central proinflammatory cytokine in the pathogenesis of this IL-1Ra−/− model of spontaneous arthritis. Its intracellular signaling pathway could be useful therapeutic targets in the treatment of autoimmune arthritis.

Hyaluronate–Gold Nanoparticle/Tocilizumab Complex for the Treatment of Rheumatoid Arthritis

Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory immune disease causing the inflammation of synovial membrane and the articular cartilage destruction. In this work, hyaluronate–gold nanoparticle/Tocilizumab (HA-AuNP/TCZ) complex was prepared for the treatment of RA. AuNP was used as a drug carrier with antiangiogenic effect. TCZ is a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor and used as an immunosuppressive drug by interfering IL-6 in the pathogenesis of RA. HA is known to have cartilage-protective and lubricant effects. HA was modified with cystamine via reductive amination, which was reduced with dithiothreitol (DTT) to prepare end-group thiolated HA (HA-SH). AuNP was chemically modified with HA-SH and physically modified with TCZ. The formation of HA-AuNP/TCZ complex was corroborated by UV–vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The therapeutic effect of HA-AuNP/TCZ complex on RA was confirmed in collagen-induced art...

Up-regulation of stromal cell–derived factor 1 (CXCL12) production in rheumatoid synovial fibroblasts through interactions with T lymphocytes: Role of interleukin-17 and CD40L–CD40 interaction

Abstract: Objective Stromal cell–derived factor 1 (SDF-1) is a potent chemoattractant for memory T cells in inflamed rheumatoid arthritis (RA) synovium. This study was undertaken to investigate the effect of interleukin-17 (IL-17) and CD40–CD40L interaction on SDF-1 production in RA fibroblast-like synoviocytes (FLS). Methods Synovial fluid (SF) and serum levels of SDF-1 in RA patients were measured by enzyme-linked immunosorbent assay (ELISA). The SDF-1 produced by cultured RA FLS was evaluated by real-time polymerase chain reaction and ELISA after FLS were treated with IL-17 and inhibitors of intracellular signal molecules. The SDF-1 level was also determined after FLS were cocultured with T cells in the presence and absence of IL-17. Results Concentrations of SDF-1 in the sera and SF were higher in RA patients than in osteoarthritis patients, although the increase in the serum levels did not reach statistical significance. The production of SDF-1 in RA FLS was enhanced by IL-17 stimulation. This effect of IL-17 was blocked by inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), NF-κB, and activator protein 1 (AP-1). When FLS were cocultured with T cells, SDF-1 production was up-regulated, especially in the presence of IL-17, but FLS were inhibited by neutralizing anti–IL-17 and anti-CD40L antibodies. Addition of RA SF to cultured RA FLS significantly up-regulated SDF-1 messenger RNA expression, which was hampered by pretreatment with anti–IL-17 antibody. Conclusion SDF-1 is overproduced in RA FLS, and IL-17 could up-regulate the expression of SDF-1 in RA FLS via pathways mediated by PI 3-kinase, NF-κB, and AP-1. Our findings suggest that inhibition of the interaction between IL-17 from T cells and SDF-1 in FLS may provide a new therapeutic approach in RA.

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Monocyte chemoattractant protein-1 (MCP-1): an overview.

Abstract: Chemokines constitute a family of chemoattractant cytokines and are subdivided into four families on the basis of the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils, and lymphocytes, as well as in inducing chemotaxis through the activation of G-protein-coupled receptors. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in various diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.

A cytokine-mediated link between innate immunity, inflammation, and cancer

Abstract: It has been established that cancer can be promoted and/or exacerbated by inflammation and infections. Indeed, chronic inflammation orchestrates a tumor-supporting microenvironment that is an indispensable participant in the neoplastic process. The mechanisms that link infection, innate immunity, inflammation, and cancer are being unraveled at a fast pace. Important components in this linkage are the cytokines produced by activated innate immune cells that stimulate tumor growth and progression. In addition, soluble mediators produced by cancer cells recruit and activate inflammatory cells, which further stimulate tumor progression. However, inflammatory cells also produce cytokines that can limit tumor growth. Here we provide an overview of the current understanding of the role of inflammation-induced cytokines in tumor initiation, promotion, and progression.

Regulatory T Cells

Abstract: Despite the skepticism that once prevailed among immunologists, it is now widely accepted that the normal immune system harbors a T-cell population, called regulatory T cells (Treg cells), specialized for immune suppression. It was first shown that depletion of a T-cell subpopulation from normal rodents produced autoimmune disease. Search for a molecular marker specific for such autoimmune-preventive Treg cells has revealed that the majority, if not all, of them constitutively express the CD25 molecule as depletion of CD25+CD4+ T cells spontaneously evokes autoimmune disease in otherwise normal rodents. The expression of CD25 by Treg cells has made it possible to delineate their developmental pathways, in particular their thymic development, and establish simple in vitro assay for assessing their suppressive activity. The marker and the in vitro assay have helped to identify human Treg cells with similar functional and phenotypic characteristics. Recent efforts have shown that natural Treg cells specifically express the transcription factor Foxp3 and that mutations of the Foxp3 gene produce a variety of immunological diseases in humans and rodents. Specific expression of Foxp3 in natural Treg cells has enabled their functional and developmental characterization by genetic approach. These studies altogether have provided firm evidence for Foxp3+CD25+CD4+ Treg cells as an indispensable cellular constituent of the normal immune system for establishing and maintaining immunologic self-tolerance and immune homeostasis. Treg cells are now within the scope of clinical use to treat immunological diseases and control physiological and pathological immune responses.

Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells.

Abstract: Interleukin 17 (IL-17)-producing CD4(+) helper T cells (T(H)-17 cells) have been linked to host defense and autoimmune diseases. In mice, the differentiation of T(H)-17 cells requires transforming growth factor-beta and IL-6 and the transcription factor RORgammat. We report here that for human naive CD4(+) T cells, RORgammat expression and T(H)-17 polarization were induced by IL-1beta and enhanced by IL-6 but were suppressed by transforming growth factor-beta and IL-12. Monocytes and conventional dendritic cells, but not monocyte-derived dendritic cells activated by microbial stimuli, efficiently induced T(H)-17 priming, and this function correlated with antigen-presenting cell production of IL-1beta and IL-6 but not IL-12. Our results identify cytokines, antigen-presenting cells and microbial products that promote the polarization of human T(H)-17 cells and emphasize an important difference in the requirements for the differentiation of T(H)-17 cells in humans and mice.