• Clinical and Experimental Pediatrics
• /
• v.50 no.12
• /
• pp.1165-1172
• /
• 2007

Self/non-self discrimination and unresponsiveness to self is the fundamental properties of the immune system. Self-tolerance is a state in which the individual is incapable of developing an immune response to an individual's own antigens and it underlies the ability to remain tolerant of individual's own tissue components. Several mechanisms have been postulated to explain the tolerant state. They can be broadly classified into two groups: central tolerance and peripheral tolerance. Several mechanisms exist, some of which are shared between T cells and B cells. In central tolerance, the recognition of self-antigen by lymphocytes in bone marrow or thymus during development is required, resulting in receptor editing (revision), clonal deletion, anergy or generation of regulatory T cells. Not all self-reactive B or T cells are centrally purged from the repertoire. Additional mechanisms of peripheral tolerance are required, such as anergy, suppression, deletion or clonal ignorance. Tolerance is antigen specific. Generating and maintaining the self-tolerance for T cells and B cells are complex. Failure of self-tolerance results in immune responses against self-antigens. Such reactions are called autoimmunity and may give rise to autoimmune diseases. Development of autoimmune disease is affected by properties of the genes of the individual and the environment, both infectious and non-infectious. The host's genes affect its susceptibility to autoimmunity and the environmental factors promote the activation of self-reactive lymphocytes, developing the autoimmunity. The changes in participating antigens (epitope spreading), cells, cytokines or other inflammatory mediators contribute to the progress from initial activation to a chronic state of autoimmune diseases.

• IMMUNE NETWORK
• /
• v.6 no.1
• /
• pp.6-12
• /
• 2006

Background: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. Methods: Signal sequence trap was used to find stress novel secretory protein from HP A-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. Results: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. Conclusion: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.18 no.1
• /
• pp.172-178
• /
• 2004

To investigated the effects of Kwibi-tang water extract (KBT) on the non-specific immune response in C57BL/6 mice stressed by immobilization, we evaluated the changes in the contents of serum histamine and corticosterone and the phagocytic activity of macrophages. The level of serum histamine and corticosterone was determined with spectrofluorometer. The cell viability was determined by a MTT assay method. The subpolpulation of lymphocytes was determined by a flow cytometry. The phagocytic activity was determined with luminometer. KBT decreased the serum level of histamine and corticosterone increased by immobilization stress. Also, KBT enhanced the phagocytic activity and decreased the level of nitric oxde in murine peritoneal macrophages decreased by immobilization stress. These results indicate that KBT may be useful for the prevention and treatment of stress via suppression of serum histamine and corticosterone level and enhancement of the non-specific immune response.

• Archives of Pharmacal Research
• /
• v.28 no.3
• /
• pp.343-350
• /
• 2005

Gamma radiation causes suppression of the immune function, and immune properties are related to cytokine production. In the present study, the polysaccharide, Ginsan, purified from an ethanol-insoluble fraction of Ginseng (Panax ginseng C.A. Meyer, Araliaceae) water extract was studied to assess its effects on the immunosuppressive activities of gamma radiation. Gin­san was found to stimulate murine normal splenocytes by inducing the mRNA expressions of Th1 and Th2 type cytokines, and also restore the mRNA expression of IFN-$/gamma$, Th1 cytokine, after its inhibition by whole-body gamma irradiation. Therefore, Ginsan was found to restore the T lymphocytes function that had been suppressed by gamma irradiation in allogenic MLR (mixed lymphocyte reactions). However, Ginsan exhibited no excessive stimulatory effects on the control group. The above results indicated that Ginsan may constitute a new noble agent for the improvement of gamma radiation-induced immunosuppression.

• Biomolecules & Therapeutics
• /
• v.28 no.1
• /
• pp.1-17
• /
• 2020

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exert suppressive function on the immune response. MDSCs expand in tumor-bearing hosts or in the tumor microenvironment and suppress T cell responses via various mechanisms, whereas a reduction in their activities has been observed in autoimmune diseases or infections. It has been reported that the symptoms of various diseases, including malignant tumors, can be alleviated by targeting MDSCs. Moreover, MDSCs can contribute to patient resistance to therapy using immune checkpoint inhibitors. In line with these therapeutic approaches, diverse oligonucleotide-based molecules and small molecules have been evaluated for their therapeutic efficacy in several disease models via the modulation of MDSC activity. In the current review, MDSC-targeting oligonucleotides and small molecules are briefly summarized, and we highlight the immunomodulatory effects on MDSCs in a variety of disease models and the application of MDSC-targeting molecules for immuno-oncologic therapy.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.05a
• /
• pp.15-20
• /
• 2003

Molecular immunological methods are extensively applied to toxicological investigations. Furthermore, various immunological markers have been developed to substantiate molecular mechanisms of xenobiotics-mediated immunotoxicities. We discuss molecular immunological approach to evaluate lead (Pb)-induced immune alteration resulting in suppression of IFN${\gamma}$ production, and its value for establishing useful immunotoxicological markers.(omitted)

• Proceedings of the Ginseng society Conference
• /
• 2007.05a
• /
• pp.25-25
• /
• 2007

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.11b
• /
• pp.149-150
• /
• 2002

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, reproductive toxicity and developmental toxicity.(omitted)

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.294.1-294.1
• /
• 2002

The effects of estradiol and its metabolites on the regulation of CYP1A1 expression. K.E. Joung and Y.Y. Sheen College of Pharmacy, Ewha womans University, Seoul. 120-750, Korea 2, 3.7.8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity. immune suppression. and reproductive and developmental toxicity. (omitted)

• Bulletin of the Korean Chemical Society
• /
• v.32 no.11
• /
• pp.3893-3898
• /
• 2011

Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-${\kappa}B$ transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-${\kappa}B$ activity by inducing $I{\kappa}B{\alpha}$ polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.