Su Wol Chung

Bio: Su Wol Chung is an academic researcher from Chonnam National University. The author has contributed to research in topics: Interleukin 12 & Cytokine. The author has an hindex of 15, co-authored 17 publications receiving 1190 citations. Previous affiliations of Su Wol Chung include Brigham and Women's Hospital.

Enhancement of interleukin-4 production in activated CD4+ T cells by diphthalate plasticizers via increased NF-AT binding activity.

Abstract: Background: Diethylhexyl phthalate (DEHP) and diisononyl phthalate (DINP), two commonly used plasticizers in flexible polyvinylchloride formulations, have potentially adverse effects on human health. However, the influence of these diphthalates on allergic responses remains unclear. In this study we examined the effects of DEHP and DINP on IL-4 production in CD4+ T cells and the level of IgE in sera, critical hallmarks associated with allergic diseases. Methods: Mouse T cells were exposed to two diphthalates in vitro and in vivo. The levels of IL-4 and IgE were determined by ELISA, and the degree of NF-AT activation was determined by IL-4 gene promoter assay and electrophoretic mobility shift assay. Results and Discussion: Both DEHP and DINP significantly enhanced IL-4 production in activated CD4+ T cells in a concentration-dependent manner. Treatment with DEHP or DINP in vivo resulted in a significant increase of IL-4 production in CD4+ T cells and of IgE levels in sera. Furthermore, DEHP and DINP enhanced the activation of IL-4 gene promoter in EL4 T cells and the enhancing effect mapped to a region in the IL-4 promoter containing binding sites for a transcription factor, NF-AT. The activation of T cells resulted in markedly enhanced binding activities to the NF-AT site, which significantly increased upon addition of DEHP or DINP, indicating that NF-AT was involved in the enhancing effect of DEHP and DINP on IL-4 production. These findings suggest that both DEHP and DINP enhance allergic responses by enhancement of IL-4 production in CD4+ T cells via stimulation of NF-AT-binding activity.

Inhibition of Interleukin-4 Production in CD4+ T Cells by Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) Ligands: Involvement of Physical Association between PPAR-γ and the Nuclear Factor of Activated T Cells Transcription Factor

Abstract: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been implicated in the regulation of multiple inflammatory processes. However, little is known of PPAR-gamma in the regulation of interleukin (IL)-4 expression in T cells. In this study, the effects of PPAR-gamma ligands on production of IL-4, a pro-inflammatory cytokine associated with the pathophysiology of allergic diseases, were investigated. 15-Deoxy-Delta12,14 prostaglandin J2 (15d-PGJ2) and ciglitazone, two representative PPAR-gamma ligands, significantly inhibited IL-4 production in both antigen-stimulated primary CD4+ T cells and the phorbol 12-myristate 13-acetate (PMA)/ionomycin-activated EL-4 T cell line. 15d-PGJ2 and ciglitazone inhibited the activation of IL-4 gene promoter in EL-4 T cells transiently transfected with IL-4 promoter/reporter constructs, and the repressive effect mapped to a region in the IL-4 promoter containing binding sites for nuclear factor of activated T cells (NF-AT). The activation of T cells by PMA/ionomycin resulted in a marked enhancement of the binding activities to the NF-AT site that was significantly inhibited by the addition of PPAR-gamma ligands. In cotransfected EL-4 T cells, PPAR-gamma also inhibited the activation of the IL-4 promoter at multiple NF-AT sites in a ligand-dependent manner. NF-ATc1 bound PPAR-gamma both in vivo and in vitro, and the interaction interfaces involved the Rel similarity domain of NF-ATc1. In cotransfections of HeLa cells, PPAR-gamma inhibited the NF-ATc1 transactivation in a ligand-dependent manner. Coexpression of p300 or AP-1 relieved the PPAR-gamma ligand-mediated inhibition of the NF-AT transactivation. From these results, we propose that PPAR-gamma ligand-mediated suppression of IL-4 production in CD4+ T cells may involve both inhibition of the NFAT-DNA interactions and competitive recruitment of transcription integrators between NF-AT and PPAR-gamma.

Anticancer potential of curcumin: preclinical and clinical studies.

Abstract: Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF- κB, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies. Curcumin, derived from turmeric (vernacular name: Haldi), is a rhizome of the plant Curcuma longa. The medicinal use of this plant has been documented in Ayurveda (the Indian

Curcumin: The Indian solid gold

Abstract: Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells.

Abstract: To prime immune responses, dendritic cells (DCs) need to be activated to acquire T cell stimulatory capacity. Although some stimuli trigger interleukin 12 (IL-12) production that leads to T helper cell type I (TH1) polarization, others fail to do so and favor TH2 polarization. We show that after activation by lipopolysaccharide, DCs produced IL-12 only transiently and became refractory to further stimulation. The exhaustion of cytokine production impacted the T cell polarizing process. Soon after stimulation DCs primed strong TH1 responses, whereas at later time points the same cells preferentially primed TH2 and nonpolarized T cells. These findings indicate that during an immune response, T cell priming conditions may change in the lymph nodes, suggesting another mechanism for the regulation of effector and memory T cells.

Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-|[gamma]| and RelA

Abstract: The human gut microflora is important in regulating host inflammatory responses and in maintaining immune homeostasis. The cellular and molecular bases of these actions are unknown. Here we describe a unique anti-inflammatory mechanism, activated by nonpathogenic bacteria, that selectively antagonizes transcription factor NF-kappaB. Bacteroides thetaiotaomicron targets transcriptionally active NF-kappaB subunit RelA, enhancing its nuclear export through a mechanism independent of nuclear export receptor Crm-1. Peroxisome proliferator activated receptor-gamma (PPAR-gamma), in complex with nuclear RelA, also undergoes nucleocytoplasmic redistribution in response to B. thetaiotaomicron. A decrease in PPAR-gamma abolishes both the nuclear export of RelA and the anti-inflammatory activity of B. thetaiotaomicron. This PPAR-gamma-dependent anti-inflammatory mechanism defines new cellular targets for therapeutic drug design and interventions for the treatment of chronic inflammation.

Safety and Anti-Inflammatory Activity of Curcumin: A Component of Tumeric (Curcuma longa)

Abstract: Introduction: Tumeric is a spice that comes from the root Curcuma longa, a member of the ginger family, Zingaberaceae. In Ayurveda (Indian traditional medicine), tumeric has been used for its medicinal properties for various indications and through different routes of administration, including topically, orally, and by inhalation. Curcuminoids are components of tumeric, which include mainly curcumin (diferuloyl methane), demethoxycurcumin, and bisdemethoxycurcmin. Objectives: The goal of this systematic review of the literature was to summarize the literature on the safety and anti-inflammatory activity of curcumin. Methods: A search of the computerized database MEDLINE™ (1966 to January 2002), a manual search of bibliographies of papers identified through MEDLINE, and an Internet search using multiple search engines for references on this topic was conducted. The PDR for Herbal Medicines, and four textbooks on herbal medicine and their bibliographies were also searched. Results: A large number of studies...