• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.241-247
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• 1998

Ketoconazole is an imidazole antifungal agent which inhibits the biosynthesis of fungal cellmembrane ergosterol and has immunosuppressive properties in vitro. Biphenyl dimethyl dicarboxylate (PMC) has been utilized for antioxidative action and for liver-protective purposes. Studies were undertaken to investigate effects of biphenyl dimethyl dicarboxylate (PMC) on the immunosuppression of ketoconazole in ICR mice. In the combination of PMC and ketoconazole, as compared with the treatment of ketoconazole alone, there were significant increases in activities of natural killer (NK) cells and phagocytes along with circulation leukocytes. The elevation of serum glutamic-pyruvic transaminase (S-GPT) and total protein levels caused by ketoconazole were reduced by the combination of PMC and ketoconazole. In addition, lower serum albumin and albumin/globulin (A/G) ratio were also increased to normal level.

• Proceedings of the Korean Biophysical Society Conference
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• 1996.07a
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• pp.9-9
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• 1996

The immunosuppressive and cell cycle arrest agent rapamycin works by binding together two proteins: the FK506 binding protein (FKBP12) and the FKBP-rapamycin associated protein (FRAP). A 2.7 $\AA$ resolution crystal structure of the triple complex of human FK506 binding protein (FKBP12), rapamycin, and FKBP12-rapamycin binding domain (FRB) of FRAP, reveals two proteins bound together through rapamycin' s ability to simultaneously occupy two different hydrophobic binding pockets. (omitted)

• Korean Journal of Veterinary Service
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• v.33 no.1
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• pp.13-21
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• 2010

Chicken anemia virus (CAV) has been recognized as an immunosuppressive agent and plays role as an etiological agent of multifactorial diseases in chicken. In this study, we investigated distribution of CAV antibody by ELISA and the virus gene by PCR in poultry farms in Jeongeup, Jeonbuk province. In the test using ELISA kit, 41 (95.3%) of 43 flocks and 88.6% of the individual chickens were positive, respectively. By PCR, 90.9% of the broiler breeders and 75.0% of White-semi breeders were found positive, respectively. All hatchery was negative by PCR. Of the clinical cases from 49 poultry flocks, 87.5% of flocks and 54.7% for each samples were found positive by ELISA, respectively. By PCR test, 21 (42.9%) of 49 flocks were positive. Major clinical signs of the infected flocks were growth retardation, femoral subcutaneous bleeding, depression, limping, and continuing selection. The genetic analysis of separate N genes of CAV showed highly homologous each other. The nucleotide sequence of field isolates had homology ranged from 99.9% to 97.5% with Chinese strains, and 99.9% to 99.6% with Japanese strain. Phylogenetic analysis based on the N gene of CAV isolates showed the closely relation with Chinese strains. The results of this survey could be used as basic data for development of vaccine.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.601-610
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• 2003

Biotin is a water-soluble vitamin used as a skin conditioning agent and promotes the formation of intercellular lipid layers through increased lipid synthesis, which improves the skin's natural barrier function. The anti-inflammatory effects of biotin have been investigated using in vitro assay models, such as MTT assay, measurements of concentrations of nitric oxide(NO), prostaglandin E2(PGE$_2$), and inhibition rate of 5-lipoxygenase(5-LOX). In comparison with biotin, other plant extracts were tested at the same time which were kudzu vine extract, sage extract, paeonia extract, and dipotassium glycyrrhetinate. Nitric oxide is a signal molecule with functions such as neurotransmission, local vascular relaxation, and anti-inflammation in many physiological and pathological processes. NO can cause apoptosis and necrosis of target cells such as keratinocytes and is generated from L-arginine by nitric oxide synthase (NOS). Prostanoids, including prostaglandins and thromboxanes, are generated by the phospholipase $A_2$/cyclooxygenase(COX) pathway, and leukotrienes are generated by the 5-lipoxygenase pathway from arachidonic acid. Prostaglandin E2 recently have been shown to be beneficial in the resolution of tissue injury and inflammation, also has been implicated as an immunosuppressive agent and plasma levels of PGE$_2$ are elevated in patients sustaining thermal injury. Lipoxygenase metabolites from arachidonic acid have been implicated in inflammation, anti-inflammatory activity of the raw materials was evaluated in vitro by the offered inhibition of lipoxygenase.

• Journal of Radiation Protection and Research
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• v.48 no.1
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• pp.1-8
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• 2023

Background: The purpose of this study is to evaluate the immunosuppressive and antioxidant effects of a novel radioprotective agent using the vitamin E derivative 2-(alpha-D-glucopyranosyl)methyl-2,5,7,8-tetramethylchroman-6-ol (TMG) and its effect on tumors, and to study its usefulness. Materials and Methods: In this study, C57BL/6NCrSlc mice were divided into four groups (control, TMG, radiation therapy [RT], and RT+TMG), using 10 mice in each group. In the TMG and 2 Gy+TMG groups, 500 mg/kg TMG was administered. Two groups (2 Gy and 2 Gy+TMG) among RT and RT+TMG groups were irradiated with 2 Gy in a single fraction, while the other two groups (6 Gy and 6 Gy+TMG) were irradiated locally with 6 Gy in three fractions. Results and Discussion: TMG positively affected CD4+ and CD8+ T lymphocytes. Tumor volumes and growth inhibition rates were compared. In order to evaluate how TMG administration affected tumor growth, Ehrlich cancer cells were injected into the thigh of mice, and the tumor volume and growth suppression rate were compared. Not only RT but also TMG alone inhibited tumor growth. If RT conducted to the mice with TMG, TMG could increase the number of leukocytes, primarily that of lymphocytes. TMG also inhibited tumor growth in addition to RT. Tumor growth was significantly inhibited in the 6 Gy+TMG group. Conclusion: In conclusion, TMG exerted an immunopotentiating effect mainly by increasing the white blood cell numbers including that of lymphocytes. In addition to RT, TMG also inhibited tumor growth. Therefore, TMG is considered to be a useful radioprotective agent in radiotherapy without tumor growth induction.

• Parasites, Hosts and Diseases
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• v.40 no.3
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• pp.131-138
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• 2002

The cyclophilins (Cyps) are family members of proteins that exhibit peptidylprolyl cis-trans isomerase (PPIase, EC 5.2.1.8) activity and bind the immunosuppressive agent cyclosprin A (CsA) in varying degrees. During the process of random sequencing of a cDNA library made from Giardia intestinalis WB strain, the cyclophilin gene (gicypl) was isolated. An open reading frame of gicyp1 gene was 576 nucleotides, which corresponded to a translation product of 176 amino acids (Gicypl). The identity with other Cyps was about 58-71%. The 13 residues that constituted the CsA binding site of human cyclophilin were also detected in the amino acid sequence of Gicypl, including tryptophan residue essential for the drug binding. The single copy of the gicypl gene was detected in the G. intestinalis chromosome by southern hybridization analysis. Recombinant Gicyp 1 protein clearly accelerated the rate of cis ${\rightarrow}$ trans isomerization of the peptide substrate and the catalysis was completely inhibited by the addition of $0.5{\;}{\mu}M$ CsA.

• Fisheries and Aquatic Sciences
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• v.19 no.9
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• pp.35.1-35.6
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• 2016

Gliotoxin has been recognized as an immunosuppressive agent for a long time. Recently, it was reported to have antitumor properties. However, the mechanisms by which it inhibits tumors remain unclear. Here, we showed that gliotoxin isolated from the marine fungus Aspergillus fumigatus inhibited proliferation and induced apoptosis in HT1080 human fibrosarcoma cells. Gliotoxin repressed phosphorylation-dependent degradation of $I{\kappa}B-{\alpha}$, an antagonist of nuclear factor kappa B ($NF-{\kappa}B$), which is a known tumor-promoting factor. This coincided with a decrease in nuclear import of $NF-{\kappa}B$, suggesting its signaling activity was impaired. Moreover, gliotoxin increased intracellular reactive oxygen species (ROS). Since ROS have been known to inhibit $NF-{\kappa}B$, this may also contribute to gliotoxin's antitumorigenic effects. These results suggest that gliotoxin suppressed the activation of $NF-{\kappa}B$ by inhibiting phosphorylation and degradation of $I{\kappa}B-{\alpha}$ and by increasing ROS, which resulted in apoptosis of HT1080 cells. Cumulatively, gliotoxin is a promising candidate antagonist of $NF-{\kappa}B$, and it should be investigated for its possible use as a selective inhibitor of human fibrosarcoma cells.

• Toxicological Research
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• v.20 no.4
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• pp.293-298
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• 2004

Background: Crohn's disease is characterized by a chronic relapsing inflammation of the bowel. Gliotoxin has been known to play strong immunosuppressive properties, while mechanisms for its anti-inflammatory actions are not completely understood. Here, we investigated the effects of gliotoxin in trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, an animal model of Crohn's disease. Results: Gliotoxin dramatically improved clinical and histopathological symptoms in accompanied with reduced expression of TNF-$\alpha$, IL-1$\beta$, and ICAM-1 protein levels in TNBS induced colitis. Interestingly Gliotoxin induced Heme oxygenase-1 (HO-1) and the HO-1 inducer cobalt protoporphyrin IX (CoPPIX) completely mimicked the protective effects of gliotoxin in TNBS induced colitis mice. In contrast, the HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) could reverse the anti-inflammatory effects of gliotoxin and CoPPIX. Conclusions: Gliotoxin is a potential therapeutic agent targeting for the treatment of Crohn's disease by inducing HO-1.

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

• Childhood Kidney Diseases
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• v.14 no.1
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• pp.10-21
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• 2010

The overall prognosis of Henoch-Schoenlein purpura (HSP) is favorable, but severe nephritis has a high risk of progression to end stage renal failure. Recent studies emphasize the importance of early treatment in children with severe HSP nephritis, but the treatment of severe HSP nephritis still remains controversial due to the rarity of randomized controlled studies in this field. Nevertheless, several intensive therapies, such as intravenous high-dose methylprednisolone pulse, immunosuppressive/cytotoxic drugs, fibrinolytic therapy, anticoagulants, antiplatelet agent and plasma exchange, have been used in children with severe HSP nephritis. In this review, we focus on the treatment of severe HSP nephritis in children.