• Korean Journal of Veterinary Research
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• v.40 no.2
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• pp.311-323
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• 2000

Immunosuppressive effects of reticuloendotheliosis virus (REV) infection in chickens were investigated. Primary antibody responses to Newcastle disease virus (strain B1) and sheep red blood cells were significantly low in chickens inoculated with the local isolate 89-74 of REV compared to those of uninfected chickens. In chickens infected with REV strain T or 89-74, blastogenesis of spleen cells and peripheral blood lymphocytes (PBL) to concanavalin A (Con A) was severely suppressed. When specific pathogen free (SPF) chickens were inoculated with the isolate, the suppressive effect was observed up to 7 weeks of age while, in the contact infected chickens, the suppression was absent. Similar suppressive effects were observed in chickens inoculated with REV strain T at 2, 3 and 4 weeks of age. When spleen cells or PBL from uninfected chickens were co-cultured with spleen cells or PBL from chickens infected with REV at 1 day-old or 2 week-old, the blastogenesis of the normal cells was suppressed. The suppressive effect of PBL from REV-infected chickens on normal lymphocytes was abrogated by the treatment with trypsin. However the suppressive activity of the REV-infected PBL was not influenced at removing machrophage from the cell suspension by incubation in plastic petri dishes. In addition to the immunosuppression, chickens infected with the REV isolate showed abnormal feather development (nakanuke), anemia, paralysis and retarded growth. Three out of 11 chickens inoculated with the isolate at day-old died between 6 and 9 weeks of age by bacterial infections.

• Microbiology and Biotechnology Letters
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• v.38 no.4
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• pp.475-480
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• 2010

Actinomycetes are Gram-positive soil bacteria and one of the most important industrial microorganisms due to superior biosynthetic capabilities of many valuable secondary metabolites as well as production of various valuable bioconversion enzymes. Among them are cytochrome P450 hydroxylase (CYP), which are hemoproteins encoded by a super family of genes, are universally distributed in most of the organisms from all biological kingdoms. Actinomycetes are a rich source of soluble CYP enzymes, which play critical roles in the bioactivation and detoxification of a wide variety of metabolite biosynthesis and xenobiotic transformation. Cyclosporin A (CyA), one of the most commonly-prescribed immunosuppressive drugs, was previously reported to be hydroxylated at the position of 4th N-methyl leucine by a rare actinomycetes called Sebekia benihana, leading to display different biological activity spectrum such as loss of immunosuppressive activities yet retaining hair growth-stimulating side effect. In order to improve this regio-selective CyA hydroxylation in S. benihana, previously-identified several secondary metabolite up-regulatory genes from Streptomyces coelicolor and S. avermitilis were heterologously overexpressed in S. benihana using an $ermE^*$ promoter-containing Streptomyces integrative expression vector. Among tested, SCO4967 encoding a conserved hypothetical protein significantly stimulated region-specific CyA hydroxylation in S. benihana, implying that some common regulatory systems functioning in both biosynthesis and bioconversion of secondary metabolite might be present in different actinomycetes species.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.350-356
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• 2017

We previously reported that the CopA3 peptide (LLCIALRKK, ${\small{D}}-form$) originally isolated from the Korean dung beetle has antimicrobial and immunosuppressive effects. However, the high cost of producing the synthetic peptide, especially the ${\small{D}}-form$, has limited the development of CopA3 for therapeutic purposes. Here, we investigated whether the CopA3 deletion derivative, CopA5, which is composed of only five amino acids (LLCIA) and has the ${\small{L}}-form$ structure, could inhibit the lipopolysaccharide (LPS)-induced activation of macrophages. Peritoneal exudate macrophages (PEM) were isolated from mice and exposed to LPS in the presence or absence of CopA5, and biomarkers of macrophage activation were measured. Our results revealed that LPS-induced nitric oxide (NO) production, tumor necrosis factor $(TNF)-{\alpha}$ secretion, and phagocytic activity of PEM were significantly inhibited by CopA5 treatment. Similar to CopA3, the structurally modified CopA5 peptide had no cell toxicity (as assessed by measurement of cell viability loss and apoptosis) in PEM. Moreover, the LPS-induced upregulation of the activating phosphorylation of signal transducer and activator of transcription 1 (STAT1) was markedly inhibited by CopA5 treatment. These results suggest that, similar to CopA3, CopA5 inhibits macrophage activation by inhibiting STAT1 phosphorylation and blocking the release of NO and $TNF-{\alpha}$. CopA5 may therefore prove therapeutically useful in the realm of immune suppression.

• Natural Product Sciences
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• v.13 no.1
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• pp.33-39
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• 2007

Eleven polyhydroxyursane triterpenoids (PHUTs) were tested to determine their cytoprotective, immunosuppressive and anti-inflammatory effects. To compare the bioactivities of $19{\alpha}$-hydroxyursane-type triterpenoids {23-hydroxytormentic acid (6), its methyl ester (7), tormentic acid (8), niga-ichigoside $F_1$ (9),euscaphic acid (10) and kaji-ichigoside $F_1$ (11)} of the Rosaceae crude drugs (Rubi Fructus and Rosa rugosae Radix) with PHUTs possessing no $19{\alpha}-hydroxyl$ of Centella asiatica (Umbelliferae), the four PHUTs, asiaticoside (1), madecassoside (2), asiatic acid (3), and madecassic acid (4) were isolated from C. asiatica and 23-hydroxyursolic acid (5) from Cussonia bancoensis. Cytoprotective effects were assessed by measuring cell viabilities against cisplatin-induced cytotoxocity in $LLC-PK_1$, cells (proximal tubule, pig kidney) to determine whether these agents have protective effects against nephrotoxicity caused by cisplatin. The inhibitory effect of 11 PHUTS on nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ were evaluated by measuring nitrite accumulation in lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cells, and their anti-inflammatory effects were tested in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model. Six MHUTs (compounds 1, 2, 4, 6, 10, and 11) exhibited higher cell viabilities during cisplatin-induced cytotoxicity testing even at a concentration of $200\;{\mu}g/ml$ than cisplatin only-treated group, suggesting that ese compounds have the potentcytoprotective efffcts. Compounds 1 and 3 of the C. asiatica and niga-ichigoside $F_1$ exhibited no inhibitory effect on NO and/or $PGE_2$ production whereas other PHUTs produced mild to significant NO and/or $PGE_2$ production.The four compounds (2, 5, 9, and 10) potently inhibited mouse ear edema induced by TPA whereas two compounds (1 and 3) had no activity in this test. These results suggest that many PHUTs are potentchemopreventives. Structure-activity relationship (SAR) was also discussed in each assay with regard to the significant role of OHs at the position of 2, 3, 6, 19, and 23 and to the glycoside linkage at the 28-carboxyl.

• YAKHAK HOEJI
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• v.58 no.2
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• pp.81-90
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• 2014

In order to determine the functional benefits of Cordyceps militaris in the immune system, we examined the immunomodulatory activities of C. militaris using an immunocompromised C57BL/6 mice, mouse spleen cells, RAW 264.7 macrophage cells, and A549 lung carcinoma cells. Mice were injected intraperitioneally with an immunosuppressive drug, cyclophosphamide, and then administered orally with 30, 100 and 300 mg/kg of 50% ethanol extract of C. militaris (CME 30, CME 100 and CME 300) for 14 days. CME increased splenocyte proliferation and natural killer (NK) cell activity compared to 3% hydroxypropyl methylcellulose-treated control mice. CME also increased the production of Th1 cytokines, IL-2 and TNF-${\alpha}$ in spleen cells isolated from CME-injected mice and in vitro, which suggested the enhanced cellular immunity in response to CME. CME also increased splenocyte proliferation, NK cell activity, and IL-2 and TNF-${\alpha}$ production compared to 1 ${\mu}M$ methotrexate-treated spleen cells in vitro. We examined whether C. militaris regulates the production of inflammatory mediators in LPS-stimulated RAW 264.7 cells. CME inhibited LPS-induced NO production and iNOS expression in a dose dependent manner, while COX-2 expression was remained unchanged. In addition, CME also has free radical scavenging activity, indicating its antioxidant activity. These results indicate that C. militaris enhances immune activity by promoting immune cell proliferation and cytokine production.

• Genomics & Informatics
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• v.6 no.4
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• pp.227-230
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• 2008

Compounds of polyketide origin possess a wealth of pharmacological effects, including antibacterial, antifungal, antiparasitic, anticancer and immunosuppressive activities. Many of these compounds and their semisynthetic derivatives are used today in the clinic. Most of the gene clusters encoding commercially important drugs have also been cloned and sequenced and their biosynthetic mechanisms studied in great detail. The area of biosynthetic engineering of the enzymes involved in polyketide biosynthesis has recently advanced and been transferred into the industrial arena. In this work, we introduce a computational system to provide the user with a wealth of information that can be utilized for biosynthetic engineering of enzymes involved in post-PKS tailoring steps. Post-PKS tailoring steps are necessary to add functional groups essential for the biological activity and are therefore important in polyketide biosynthesis.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.214-217
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• 2002

Cyclosporin A (CSA) is a poorly water-soluble cyclic peptide comprising 11 amino acids. It inhibits T-lymphocyte function that plays an important role in the induction of immune response. The potent immunosuppressive activity of CSA has been used for the prevention of rejection following transplantation of liver, kidney and bone marrow, etc. The use of CSA has been often limited by several disadvantages including low bioavailability, narrow therapeutic window, nephrotoxicity, hepatotoxicity and neurotoxicity. Moreover, CSA injection is limited to patients who are unable to take the oral preparations, because it has a risk of anaphylactic shock and nephrotoxicity due to Cremophor EL$\textregistered$, a solubilizing agent used in the commercial intravenous formulation. Owing to above mentioned disadvantages of commercial products, there is a great interest in the development of the alternative dosage forms. (omitted)

• Mycobiology
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• v.33 no.3
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• pp.158-162
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• 2005

The immunomodulatory effect of aqueous extract of Inonotus obliquus, called as Chaga, was tested on bone marrow cells from chemically immunosuppressed mice. The Chaga water extract was daily administered for 24 days to mice that had been treated with cyclophosphamide (400 mg/kg body weight), immunosuppressive alkylating agent. The number of colony-forming unit (CFU)-granulocytes/macrophages (GM) and erythroid burst-forming unit (BFU-E), increased almost to the levels seen in non-treated control as early as 8 days after treatment. Oral administration of the extract highly increased serum levels of IL-6. Also, the level of $TNF-{\alpha}$ was elevated by the chemical treatment in control mice, whereas was maintained at the background level in the extract-treated mice, indicating that the extract might effectively suppress $TNF-{\alpha}$ related pathologic conditions. These results strongly suggest the great potential of the aqueous extract from Inonotus obliquus as immune enhancer during chemotherapy.

• Journal of Chest Surgery
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• v.11 no.1
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• pp.12-17
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• 1978

Rifampicin has been widely hailed as the most effective antituberculosis antibiotics since the clinical use of streptomycin, but its immunosuppressive side effect was still annoying problem to be excluded. These studies were carried out to determine the effect of Tuberein-3, tuberculous bacilli extraction with water, on Rifampicin induced T-lymphocytopenia in 5 cases of pulmonary tuberculosis who have never exposed to antimetabolites or steroid compounds. After 2 weeks treatment of Rifampicin, all cases showed T-lymphocytopenia, active $13.0{\pm}2.3$ % and total $43.1{\pm}4.4$%. Followed by another 2 weeks treatment with Rifampicin combined with Tuberein-3, T-lymphocytes in peripheral blood returned to the normal limit, active $21.6{\pm}3.3$% and total $56.3{\pm}1.7$%. Tubercin-3 revealed the restoring activity of suppression of T-lymphocyte rosettes by Rifampicin.

• Biomolecules & Therapeutics
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• v.7 no.2
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• pp.127-132
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• 1999

Triazine herbicide has been reported to directly suppress the immune response. In the present study, the effect of simazine on the immune response was investigated. Splenic lymphocytes were treated withmitogen (lipopolysaccaride, concanavalin A) in the presence of simazine. When simazine(300 mg/kg, 600 mg/kg) was administrated every day for 3 weeks or 4 weeks, respectively, the number of plaque forming cells (PFC) was decreased. Antibody production of IgM and IgG class was significantly decreased in splenic cells from simazine-treated animals. In addition, when animals were exposed to simazine, the susceptibility of virus infection as well as the growth of tumor cells was increased. These data suggest that simazine affected the immune function and humoral immunity impaired by simazine treatment contributed to pathological process.