• Korean Journal of Pharmacognosy
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• v.35 no.4 s.139
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• pp.330-337
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• 2004

Based on the traditional application of Carthamus tinctorious L. (CF) as a component of Korean medicinal decoctions, in the present study, we investigated in vitro an immunomodulatory activity of water extract of CF(WECF). Water extract of CF significantly increased the in vitro proliferative responses of spleen cells (SPC). However, addition of WECF during anti-CD3 activation resulted in a significant decrease in SPC proliferation. Flow cytometric analysis showed that WECF addition chanced T and B cell frequencies in anti-CD3-activated spleen cell populations. Using purified cells, it was revealed that WECF is mitogenic to B cells but rather inhibitory to T cell Proliferation. Upon anti-CD3 stimulation, high concentration (1 mg/ml) of WECF significantly inhibited T cell proliferation until day 2 of stimulation. At day 3, anti-CD3-activated cells exposed to WECF recovered their proliferation to the level comparable to control. Although B cell proliferation was also inhibited in proliferation at day 1, it recovered sooner and then was rather augmented by WECF at day 3. These data indicate that WECF down-regulates lymphocyte proliferation at early phase of activation but T cells are more vulnerable than B cells to WECF, However, CD4+ and CD8+ T cells did not differ in WECF-mediated immunotoxicity. Data of propidium iodide (PI) staining showed that WECF accelerates activated T cell, but not B cell, apoptosis and WECF concurrently inhibited cytokine production of activated T cells. Taken together, WECF exhibits B cell mitogenic activity and differential toxicity more pronounced to T cells, suggesting a possible in vivo application of WECF for specific control of T cells without alteration of B cell activity.

• Journal of Applied Biological Chemistry
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• v.51 no.1
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• pp.1-6
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• 2008

Estrogens, a group of steroid compounds functioning as the primary female sex hormone, play an important role in the development and progression of breast cancer. In this study, using a novel annealing control primer-based GeneFishing PCR technology, five differentially expressed genes (DEGs), expressed using 10nM mitogenic estrogens, $17{\beta}$-estradiol (E2) and $16{\alpha}$-hydroxyestrone ($16{\alpha}$-OHE1), were selected from the estrogen receptor (ER)-positive MCF-7 human breast cancer cells. The DEGs, MRPL42, TUBA1B, SSBP1, KNCT2, and RUVBL1, were identified by comparison with the known genes via direct sequencing and sequence homology search in BLAST. Quantitative real-time PCR data showed that two DEGs, tubulin ${\alpha}1b$ and kinetochore associated 2, were greater than 2-fold upregulated by E2 or $16{\alpha}$-OHE1. Both genes could be new biomarkers for the treatment and prognosis of cancers, and further study may provide insights into the molecular mechanisms underlying development and progression of breast cancer.

• Toxicological Research
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• v.15 no.1
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• pp.39-45
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• 1999

To investigate the preventive effects of melatonin (MLT) on the immunotoxicity of cadmium acetate[Cd(AC)2] in ICR mice, Mlt(10,50mg/kg as cadmium) were orally administered to mice once a day (5:00, PM) for 28 consecutive days. Cadmium(Cd) test solution was also administered at 25mg/kg of cadmium through the same route 2hr after administration of MLT daily, Mice were immunized and challenged with sheep red blood cells (SRBC). Immune functions evaluated were delayed type hypersensitivity (DTH) response, mitogenic response, and flow cytometry analysis. The results of these studies were summarized as follows ; DTH response was abnormally increased in mice treated with Cd alone. DTH response was normally depressed in mice treated with Cd plus MLT along with the increase of MLT doses. The mitogenic response of splenic T cell to Con A and that of B cells to LPS was remarkably increased by MLT treatment as compared with treatment of Cd alone In case of CD 8+ cells, the slight increase was observed in MLT treatment. Splenic T cells and B cells were significantly increased by MLT treatment as compared with treatment with Cd alone. These results suggest that MLT has significant preventive effects on the immunotoxic status induced by Cd exposure.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.507-513
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• 2000

ErbB3/HER3 is a cell surface receptor which belongs to the ErbB/HER subfamily of receptor protein tyrosine kinases. When expressed in NIH/3T3 cells, ErbB3 can form heterodimeric coreceptor with endogenous ErbB2. Among known intracellular effectors of the ErbB2/ErbB3 are mitogen-activated protein kinase (MAPK) and phosphoinositide (PI) 3-kinase. In the present study, we studied relative contributions of above two distinct signaling pathways to the heregulin-induced mitogenic response via activated ErbB3. For this, clonal NIH-3T3 cell lines expressing wild-type ErbB3 and ErbB3 mutants were stimulated with $heregulin{\beta}_1$. While cyclin D1 level was markedly high and further increased by treatment of heregulin in cells expressing wild-type ErbB3, the elimination of either Shc binding or PI 3-kinase binding lowered both levels. This result was supported by the reduction of cyclin $D_1$ expression by preteatment with MAPK kinase inhibitor or PI 3-kinase inhibitor before stimulation with heregulin. In accordance with the cyclin $D_1$ expression, elimination of either Shc binding or PI 3-kinase binding reduced the heregulin-induced DNA synthesis and cell growth rate. Our results obtained by the comparison of wild-type and ErbB3 mutants indicate that the full induction of the cell cycle progression through $G_1/S$ phase by ErbB3 activation is dependent on both Shc/MAPK and PI 3-kinase signal transduction pathways.

• Korean Journal of Medicinal Crop Science
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• v.8 no.4
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• pp.291-296
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• 2000

To evaluate the biological effects of boxthorn (Lycium chinense Mill.) extracts on the immune response systems, the mitogenic effects were tested by LPS (lipopolysaccharide) and Con A (concanavalin A) using water extracts from various parts of Lycium chinense Mill. The proliferation of B-lymphocytes which were activated by the mitogen, LPS, was markedly increased in the concentration of 0.1mg/ml to 0.5mg/ml, but inhibited in more than 0.5mg/ml. It increased only proliferation of B-lymphocytes but not that of T-lymphocytes by Con A. There was no difference between boxthorn species in immune response. Water extracts of various parts in boxthorn enhanced the humoral immune response which was related to B-lymphocytes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.896-901
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• 2006

Zingiberis rhizoma(ZB) has been used to treat a various condition and disease in traditional oriental medicine. The present study was conducted to evaluate the immunomodulatory effect of aqueous-extracted ZB(ZBE) on methotrexate (MTX)-induced immune suppression in mouse spleen cells. In spleen cell proliferation assay, ZBE enhanced mitogenic activity in mouse spleen cells. In RT-PCR, ZBE induced IL-2, IFNr and IL-6 cytokine gene expression in mouse spleen cells. In spite of MTX treatment, IL-2, IFNr and IL-6 gene expressions sustained in MTX treated spleen cells. CD45R/B220, pan B marker was slightly increased in ZBE treated mouse spleen cells. IL-6, B cell tropical cytokine, production was induced by ZBE-treated mouse spleen cells and IL-6 production was sustained on MTX-ZBE co-cultured cells. ZBE administration enhanced suNival of S-180 bearing mouse. These data indicate that ZBE has a protective effect of immune suppression caused by MTX, and ZBE may be enhance cellular and humoral function by regulate cytokine gene expression as well as the mitogenic effect on spleen cells.

• Tuberculosis and Respiratory Diseases
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• v.47 no.5
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• pp.618-628
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• 1999

Background: Cell growth is a balance between cell proliferation and cell death. Insulin-like growth factor-I(IGF-I), which binds IGF-I receptor(IGF-IR), mediates cellular proliferation as a potent mitogen. IGF binding protein-3(IGFBP-3) as a circulating major IGFBP can inhibit or enhance the effects of IGF-I on cellular growth by binding IGFs. Methods: We investigated the expressions of mRNA of IGF-I and IGF-IR by northern blot and phosphorylation of IGF-IR with the treatment of IGF-I by western blot in 3T3 fibroblast cells. The cellular proliferations of 3T3 cells with the treatments of IGF-I were evaluated using $^3H$-thymidine incorporation and MTT assay. Also to observe the effect of IGFBP-3 on cellular proliferation, 3T3 cells were treated with anti-IGFBP-3 and ${\alpha}IR_3$(monoclonal antibody to IGF-IR) alone or in combination. Results: Our results demonstrated that 3T3 cells showed mRNA expressions of IGF-I and IGF-IR and the IGF-I increased phosphorylation of IGF-IR. The treatments of 3T3 cells with IGF-I increased cellular proliferation in 5 % and 1 % seruma-containing media, not in serum-free media. The addition of anti-IGFBP-3 to neutralize IGFBP-3 showed 2-fold increase of cellular proliferation, and also co-incubation of anti-IGFBP-3 and ${\alpha}IR_3$ together showed similar increase of cellular proliferation in 3T3 cells. Interestingly, when the cells were pretreated with ${\alpha}IR_3$ for 4 hr, prior to the simultaneous addition of ${\alpha}IR_3$ and anti-IGFBP-3, anti-IGFBP-3-mediated cellular proliferation was decreased to control level. All of these results suggest that free IGF-I released from IGF-I/IGFBP-3 complex would be involved in the cellular proliferation. Conclusion: IGF-I is a mitogen through the activation of IGF-IR in 3T3 cells, and IGFBP-3 could be a potent inhibitor for IGF-I action by binding IGF-I.

• Korean Journal of Veterinary Research
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• v.28 no.1
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• pp.49-58
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• 1988

To investigate the effects of T-2 toxin on the blastogenesis of lymphocytes, pathology, hemogram and blood chemistry in the goat, the korean native goats were treated orally with T-2 toxin for 21 days with a dosage of 0.6mg per kg body weight. The results were as follows: 1. The total count of leukocytes and lymphocytes decreased significantly from 14 to 21 days after treatment. 2. Mryeloid: erythroid ratios increased significantly on days 12 after treatment. 3. Delayed-type hypersensitivity skin reactions to tuberculin were reduced predominantly. 4. T-2 toxin induced prolonged prothrombin time. 5. Mitogenic responses of lymphocytes to both lipopolysaccharide and phytohemagglutinin were significantly depressed on days 7 and 14 after treatment. 6. Treatment of T-2 toxin caused marked depletion of lymphocytes in the thymus, mesenteric lymph node, peyer's patchs and spleen.

• YAKHAK HOEJI
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• v.43 no.2
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• pp.208-213
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• 1999

The effects of five lupane-triterpenoids from leaves of two Acanthopanax spp., chiisanogenin, chisanoside and $22{\alpha}-hydroxychiisanogenin$, acakoreoside A and acantrifoside A on the mitogen-induced proliferation were investigated in vitro. T cell proliferation (TCP) to concanavalin A (Con A) and the B cell proliferation (BCP) to lipopolysaccharide (LPS) were increased by chiisanogenin. TCP to Con A was significantly increased by chiisanoside and acankoreoside A, but not affected by chiisanogenin, $22{\alpha}-hydroxychiisanogenin$ and acantrifoside A, BCP to LPS was significantly increased by acankoreoside A and acantrifoside A, and slightly increased by chiisanoside, chiisanogenin and $22{\alpha}-hydroxychiisanogenin$.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.133-133
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• 2001

It is well known that p38 mitogen-activated protein kinase (p38MAPK) participates in cellular responses to mitogenic stimuli, environmental and genotoxic stresses, and apoptotic agents. Although there are several reports on p38MAPK in relation to cell growth and apoptosis, the exact mechanism of p38MAPK-mediated cell growth regulation remains obscure.(omitted)