• Biomolecules & Therapeutics
• /
• 제16권2호
• /
• pp.126-131
• /
• 2008

Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-${\gamma}$ and TNF-${\alpha}$. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-${\gamma}$ and TNF-${\alpha}$) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제20권2호
• /
• pp.97-100
• /
• 1998

Systemic lupus erythematosus is a severe cutaneous-systemic disorder of unknown etiology, It is represented with erythematous patches on the face in a so-called butterfly distribution, and characteristically classified as an autoimmune disease with antinuclear antibodies. The autoimmune diseases such as systemic lupus erythematosus, $Sj{\ddot{o}}gren$ syndrome, rheumatoid arthritis have been associated with lymphoid malignancy - leukemia, malignant lymphoma - which could involve various organs(spleen, liver, brain, mediastinal lymph node, supraclavicular lymph node, inguinal lymph node, cervical lymph node etc.). Many authors have studied about the association of systemic lupus erythematosus and malignant lymphoma, but exact etiology is still unknown. A common viral etioloty for systemic lupus erythematosus has been suggested since virus-like particles have been found in the glomerular endothelium of patients with systemic lupus erythematosus. These oncogenic viruses may be responsible for the higher frequency of malignant lymphoma in patients with systemic lupus erythematosus. In the other theory, the causes of malignant lymphoma are the defect of immune system due to systemic lupus erythematosus and the long-term use of therapeutics for treatment of systemic lupus erythematosus. When the cellular immune system(delayed hypersensitivity) is impaired by immunosuppressive drugs, it is likely that the body is no longer able to recognize and reject malignant cells as they arise; they continue to grow and divide unhindered. The impairment of the cellular immune system may allow growth of oncogenic virus or the survival of neoplatic tissues. 47-year old female patient treated systemic lupus erythematosus with steroid and immunosuppressive drugs for 5 years visited to our hospital due to elevated mass on left upper anterior maxilla area. By performing biopsy, we diagnosed this lesion as malignant lymphoma and referred to oncologist for chemotherapy. So we report a case of malignant lymphoma due to systemic lupus erythematosus with review of literatures.

• 대한수의학회지
• /
• 제34권3호
• /
• pp.559-567
• /
• 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.

• Toxicological Research
• /
• 제16권4호
• /
• pp.317-323
• /
• 2000

The immunosuppressive effects of thirty nine chemicals chosen by their potential toxicity were evaluated using a three-step testing method. The immunotoxicity test method developed in this study consisted of three simple assays of lymphoproliferation, mixed leukocyte response, and interleukin (IL)-2 production. The first step was mitogen-induced proliferation assay. Ten chemicals showed the inhibitory effects on the mitogen (lipopolysaccharide or concanavalin A)-induced proliferation in dose-dependent manners. The second step was mixed lymphocyte response. This step crosschecked the growth-suppressive effects detected at the first step. All of 10 chemicals, which showed suppression of lymphoproliferation, also exhibited the suppressive effects on the mixed lymphocyte response in the similar range of chemical concentration. The third step was planned to determine whether or not this growth suppression was mediated through an early activation of T-cell, which could be represented with IL-2 production. Six out of 10 chemicals decreased the interleukin-2 production in the similar concentration range used in the step 1 and 2. These results suggest that those 6 chemicals might have their targets on the signal transduction path-way toward the IL-2 production. In the meantime the other 4 chemicals might have their targets after the IL-2 production signal. Taken all together, the three-step test would be simple, fast, and efficient to deter-mine whether or not the chemical has immunosuppressive effects.

• Journal of Ginseng Research
• /
• 제35권4호
• /
• pp.462-470
• /
• 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.

• Molecules and Cells
• /
• 제28권2호
• /
• pp.125-130
• /
• 2009

Tacrolimus is a widely used T cell targeted immunosuppressive drug, known as a calcineurin inhibitor. However, the exact pharmacological effects of tacrolimus on $CD4^+$ T cells have yet to be elucidated. This study investigated the effects of tacrolimus on $CD4^+$ T cell subsets. Mouse or human $CD4^+$ T cells were cultured with immobilized anti-CD3/CD28 antibodies in the presence of tacrolimus. The cell division of $CD4^+$ T cells was analyzed using a flow cytometer according to the expression of Foxp3. The gene expression patterns of tacrolimus-exposed T cells were examined by quantitative PCR. In the case of conventional $CD4^+$ T cells (Tconv cells), tacrolimus inhibited T cell receptor stimulation-induced cell division. In contrast, the cell division of regulatory $CD4^+$ T cells (Treg cells) was even promoted in the presence of tacrolimus, especially in humans. Tacrolimus did not promote conversion of Tconv to Treg cells in mice. Furthermore, tacrolimus modified the expression levels of Foxp3-regulated T cell receptor signal related-genes, PTPN22 and Itk, in human Treg cells. Immunosuppressive effect of tacrolimus may be attributed to the relatively enhanced proliferation of Treg cells in association with altered gene expression levels of TCR signaling molecules.

• Natural Product Sciences
• /
• 제26권1호
• /
• pp.59-63
• /
• 2020

This study focused on investigation of the immunosuppressive inhibitory effect through determination of IL-2 production of nine compounds (1 - 9) isolated from Chlamydomonas sp. KSF108. Among them, compounds 1, 5, and 6 displayed moderately inhibitory effects on IL-2 production at a concentration of 100 µM. In addition, the related ones including cytotoxic, anti-inflammatory, and anti-oxidant activities were also elucidated. 6 further displayed cytotoxic activity against the MCF-7 cell line, with an IC₅₀ value of 17.2 µM and 4, 6 - 7, and 9 possessed significant DPPH radical scavenging activity, with IC₅₀ values ranging from 3.1 to 4.4 µM. To the best of our knowledge, this is the first report on the bioactivity of isolated chemical constituents from the genus Chlamydomonas. Compounds 1 and 5 investigated for the first time in the activity of immunosuppressivity and 6 may come to serve as the most important marker in broad-spectrum activities of the secondary metabolites identified from C. sp. KSF108.

• Toxicological Research
• /
• 제8권2호
• /
• pp.191-203
• /
• 1992

The immunosuppressive effects of safrole were studied in female BALB/c mouse. Mice were given 100,200and 400mg safrole/kg daily for 14days and evaluated on day 15. The day 4 immunogloblin-M antibody response to T-dependent antigen, sheep red blood cells (SRBC) was inhibited dose-dependently in all doses studied. In vitro antibody response to polyclonal antigen, lipopolysaccharide (LPS) by spleen cell suspensions from safrole-treated mice were also significantly inhibited. When safrole was treated for 14days to mice, and mitogen-induced proliferation of splenocytes were assayed on day 15, there were significant suppression of responses to B-cell mitogen, LPS and T-cell mitogen concanavalin A(Con A) at a dose of 400mg safrole/kg. Direct addition of safrole on the splenocyte culture also produced a dose dependent suppression on in vitro antibody response to LPS, and mitogen-induced lymphoproliferatin at doses of 100,200,400 and 800${\mu}M$ safrole. The role of metabolic activation in safrole-induced suppression of in vitro antibody response was studied using splenocyte-hepatocyte coculture system. The suppression of in vitro antibody respose to LPS by safrole was not altered when safrole were incubated in the splenocyte-hepatocyte system for 4hr as compared with direct addition of safrole in splenocytes culture. Neither the addition of salicylamide, sulfotransferase inhibitor, nor the addation of inorganic sulfate, sulfation cofactor to the splenocyte-hepatocyte coculture, altered the suppression of antibody response by safrole. These results suggest that the immunosuppression by safrole may not by produced by the reactive metabolites which are mediated in carcinogenesis of safrole.

• Biomolecules & Therapeutics
• /
• 제16권4호
• /
• pp.351-355
• /
• 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.

• 대한수의학회지
• /
• 제40권2호
• /
• pp.311-323
• /
• 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.