• IMMUNE NETWORK
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• v.9 no.3
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• pp.84-89
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• 2009

The main stream of CD137 studies has been directed to the function of CD137 in $CD8^+$ T-cell immunity, including its anti-tumor activity, and paradoxically the immunosuppressive activity of CD137, which proves to be of a great therapeutic potential for animal models of a variety of autoimmune and inflammatory diseases. Recent studies, however, add complexes to the biology of CD137. Accumulating is evidence supporting that there exists a bidirectional signal transduction pathway for the CD137 receptor and its ligand (CD137L). CD137/CD137L interactions are involved in the network of hematopoietic and nonhematopoietic cells in addition to the well characterized antigen-presenting cell-T cell interactions. Signaling through CD137L plays a critical role in the differentiation of myeloid cells and their cellular activities, suggesting that CD137L signals trigger and sustain inflammation. The overall consequence might be that the amplified inflammation by CD137L enhances the T-cell activity together with CD137 signals by upregulating costimulatory molecules, MHC molecules, cell adhesion molecules, cytokines, and chemokines. Solving this outstanding issue is urgent and will have an important clinical implication.

• Biomolecules & Therapeutics
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• v.10 no.4
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• pp.224-229
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• 2002

Triazine herbicide has been reported to directly suppress the immune response. In the present study, we examined various functions of murine peritoneal macrophages that were isolated and stimulated with LPS after simazine (300 and 600 mg/kg body weight), a triazine herbicide, was administered every day for 4 weeks. Simazine decreased the capacity of phagocytosis, compared to those of carboxymethylcellulose (CMC)-treated control group. In addition, the production of NO and TNF-$\alpha$ was decrcased in macrophages of simazinetreated mice. However, the production of hydrogen peroxide ($H_{2}O_{2}$) was not altered. In vitro tumoricidal activity of in vivo simazine-treated macrophages was reduced against target cell. B 16 melanoma. Taken together, these results suggested that simazine might have the immunosuppressive effect on macrophages after in vivo exposure, which was related to the reduction of tumoricidal activity.

• Journal of Ginseng Research
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• v.35 no.4
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• pp.462-470
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• 2011

Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-${\gamma}$, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.351-355
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• 2008

Prodigiosin was isolated from marine bacteria Hahella chejuensis which has been recently discovered from Marado, Cheju Island, Republic of Korea. Immunosuppressive properties have been reported for prodigiosin members such as undecylprodigiosin, metacycloprodigiosin, prodigiosin, and its synthetic analogue PNU156804 (PNU). However, the effect of this agent on the function of macrophage and splenocyte has not been characterized in detail. In the present study, we examined the effects of prodigiosin for its ability to alter the function of murine macrophage and NK cell, and the proliferation of splenocytes. When thioglycollate-elicited macrophages pre-exposed to prodigiosin (1-50 ng/ml) were stimulated with LPS/IFN-$\gamma$, pretreatment with prodigiosin resulted in the inhibition of tumoricidal activity of macrophage in a concentration-dependent manner. Tumoricidal activity of NK cell was also inhibited by prodigiosin. Moreover, we found that prodigiosin was able to cause a dose-dependent inhibition of murine lymphocyte responsiveness to Con A and LPS although T-mitogenic response was the more sensitive one. Taken together, the present results point out that prodigiosin has a suppressive effect on the mitogen-induced proliferation of murine lymphocytes and the function of macrophage and NK cell.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.86-86
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• 2020

The leaves of Staphylea bumalda (S. bumalda) as a deciduous tree distributed in Korea, China and Japan are used to treat respiratory diseases or inflammation. However, there is no scientific research on the immune-enhancing activity of S. bumalda leaves. Thus, in this study, we investigated the effect of water extracts from S. bumalda leaves (SBL) on the macrophage activity using mouse macrophage cells, RAW264.7. SBL increased production of immunomodulators such as NO, iNOS, IL-1β, IL-6, TNF-α and MCP-1 in RAW264.7 cells and activated phagocytic activity of RAW264.7 cells. Inhibition of TLR2 and TLR4 blocked SBL-mediated production of immunomodulators in RAW264.7 cells. In addition, SBL-mediated production of immunomodulators was attenuated by JNK inhibition in RAW264.7 cells. SBL increased JNK phosphorylation, while Inhibition of TLR2 and TLR4 blocked SBL-mediated JNK phosphorylation in RAW264.7 cells. These results are thought to be evidence that SBL activates JNK through stimulation of TLR2 and TLR4 in macrophage to induce the production of immunomodulators. In LPS-stimulated RAW264.7 cells, SBL inhibited over-production of immunomodulators. Summarizing the results, SBL showed immunostimulatory activity under normal conditions and immunosuppressive activity under LPS-induced excessive immune response conditions.

• Korean journal of applied entomology
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• v.50 no.2
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• pp.107-113
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• 2011

Benzylideneacetone (BZA) is a compound derived from culture broth of an entomopathogenic bacterium, Xenorhabdus nematophila (Xn). Its immunosuppressive activity is caused by its inhibitory activity against eicosanoid biosynthesis. This BZA is being developed as an additive to enhance control efficacy of other commercial microbial insecticides. This study was focused on the enhancement of the immunosuppressive activity of BZA by generating its chemical derivatives toward decrease of its hydrophobicity. Two hydroxylated BZA and one sugar-conjugated BZA were chemically synthesized. All derivatives had the inhibitory activities of BZA against phospholipase $A_2$ ($PLA_2$) and phenoloxidase (PO) of the diamondback moth, Plutella xylostella, but BZA was the most potent. Mixtures of any BZA derivative with Bacillus thuringiensis (Bt) significantly increased pathogenicity of Bt. BZA also inhibited colony growth of four plant pathogenic fungi. However, BZA derivatives (especially the sugar-conjugated BZA) lost the antifungal activity. These results indicated that BZA and its derivatives inhibited catalytic activities of two immune-associated enzymes ($PLA_2$ and PO) of P. xylostella and enhanced Bt pathogenicity. We suggest its use to control plant pathogenic fungi.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.4
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• pp.1027-1031
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• 2005

In the present study, wogonin, a major flavone isolated from Scutellaria Radix were examined for its imunosuppressive activity on the 2,4-dinitro-fluorobenzene (DNFB)-induced delayed type hypersensitivity (DTH) in C3H/HeN mice. This compound inhibited selectively $TNF-\alpha$ and IL-4, but not IL-6, IL-10 and $IFN-\gamma$ on DNFB-induced Th1 and Th2 cytokines in a concentration-dependent manner. Interestingly, this compound increased the expression of heme oxygenase-1 (HO-1) in a concentration-dependent manner The above results reveal that wogonin possesses anti-inflammatory, humoral and cellular immunomodulatory, and stress reducing activities on the DNFB-induced DTH in mice and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

• YAKHAK HOEJI
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• v.37 no.1
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• pp.9-17
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• 1993

Immune functions of mice bearing Lewis Lung Carcinoma (LLC) were significantly suppressed when evaluated with mitogen responsiveness, IL-2 production and non-specific suppressor activity. Based on these immunosuppressive characteristics of LLC bearing mice, immunomodulating activates of Copolang were investigated in this model. After 15 days of LLC inoculation, Copolang was intraperitoneally administered for 7 consecutive days with doses of 20 or 200 mg/kg. Immune functions were evaluated 3 days after the final administration of Copolang. The results showed that the growth of LLC solid tumor was not inhibited by Copolang. But, mitogens-induced proliferation, IL-2 production and responsiveness to recombinant IL-2 of splenocytes were significantly augmented by the treatment of Copolang. However suppressor cell activity was not affected by Copolang. These results indicate that Copolang expresses potent immunomodulating activates through the augmentations of IL-2 production and responsiveness to recombinant IL-2, which have been generally known to be suppressed in tumor bearing mice, without affecting the growth of tumor.

• Preventive Nutrition and Food Science
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• v.4 no.4
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• pp.265-269
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• 1999

Taurine is a major $\beta$-amino acid in various tissues. Taurine transporter (TAUT) is responsible for the transportation of taurine in the cell. The transporter is affected by various stimuli to maintain its cell volume. Macrophage cell volume varies in its activated states. In our experiment, it was found that the murine macrophage cell line, RAW264.7, expressed TAUT protein in its membrane. Its transportation activities could be blocked by a $\beta$-amino acid such as $\beta$-alanine, but not by $\alpha$-amino acids in this cell line. When assessed in RAW264.7 under the influence of immunosuppressive reagents, the activity of the TAUT was decreased by the treatment of rapamycin (RM) or cyclosporin A (CsA). However when ionomycin (IM) was added to this system, TAUT activity was recovered only in CsA-treated cells in a concentration-dependent manner. In order to inhibit the voltage gated {TEX}$Ca^{+2}${/TEX} channel, calmidazolium was added to the RAW264.7 cell line. Treatment of the cell with calmidazolium completely blocked TAUT. Furthermore, addition of IM to this system recovered the activity of TAUT again. When we added phorbol myristate acetate (PMA) to the cell line, secretion of nitric oxide (NO) was increased 4-fold and the TAUT activity was decreased 5-fold. However, the addition of N-nitro L-arginine methyl ester (L-NAME), an inducible NO synthase (iNOS) inhibitor, to the PMA-treated cells, resulted in the recovery of TAUT activity. These results showed that the activity of TAUT was sensitive to the intracellular concentrations of both {TEX}$Ca^{+2}${/TEX} and NO.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.559-567
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• 1994

As a series of studies to investigate the effect of immunosuppression on Ascaris suum infection in undefinitive hosts, and a delicate relationship between host and parasite, in the present studies, SPF ICR mice were alloted to experiment 1(normal undefinitive host group) and experiment 2(immunosuppressive group treated with prednisolone acetate) and inoculated with a single dose of 1,100 embryonated A suum eggs. In normal group, the infection essentially terminates 4 days after inoculation(DAI) with the attainment of middle third-stage in the liver, although few larvae migrate to the lungs where a few advance to late third stage. In immunosuppressive group, significant numbers developed to late third-stage in liver 8 DAI. In general, increasing of the mast cells and the goblet cells in the jejunum mucosa, of T-cells in the spleen and of activity of peritoneal macrophages followed by expulsion of the worms in the both groups. Considering a series of the results, suitabilities for the host of the worm appeared the highest from rabbit, hamster and mouse in that order. In addition, patent infection of A suum in the mice was also not obviously observed in spite of immunosuppression by prednisolone acetate.