• Title/Summary/Keyword: suppressive cytokines

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Suppressive Effects of Cyanidin-3-glucoside on Th2 Cytokines Production in RBL-2H3 Cells (RBL-2H3 세포에서 Cyanidin-3-glucoside의 Th2 사이토카인 발현 억제 효과)

  • Jeong, Hwa Hyun;Yoon, Soo Jeong;Pyo, Myoung Yun
    • YAKHAK HOEJI
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    • v.57 no.5
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    • pp.309-315
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    • 2013
  • Cyanidin-3-glucoside (C3G), an anthocyanin, is one of the most widespread dietary flavonoids. We investigated the effects of C3G in PMA/ionomycin (PI)-induced RBL-2H3 cells. C3G inhibited the production of IL-4 and IL-13 and also decreased the level of mRNA in a dose-dependent manner. Furthermore, western blot analysis implied that C3G down-regulated the protein level of c-Jun, NF-ATc1 and NF-${\kappa}B$ but not c-Fos. Taken together, we suggest that C3G may have suppressive effects on Th2 cytokines and will be studied further to develop as functional foods that help alleviate allergy symptoms.

Suppressive effects of Morus alba Linne Root Bark (MRAL) on activation of MC/9 mast cells (상백피에 의한 MC/9 비만세포의 활성 억제 조절 연구)

  • Lee, Ki Jeon;Kim, Bok Kyu;Kil, Ki Jung
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.33-42
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    • 2013
  • Objective : Morus alba Linne Root Bark (MRAL) is a medicinal herb in Korean Medicine, known for its anti-inflammatory and anti-allergic properties. However, its mechanisms of action and the cellular targets have not yet been found and the study was developed to investigate the allergic suppressive effect of MRAL. The purpose of this study is to investigate the allergic suppressive effects of MRAL on activation of MC/9 mast cells. Methods : Cytotoxic activity of MRAL (50, 100, 200, 400 ${\mu}g/mL$) on MC/9 mast cells measured using EZ-Cytox cell viability assay kit (WST reagent). The levels of interleukin-5 (IL-5), IL-13 and IL-4, IL-5, IL-6, IL-13 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and real-time PCR respectively. The expression of transcription factors such as GATA-1, GATA-2, NFAT, AP-1 and NF-${\kappa}B$ p65 DNA binding activity were measured by western blot and electrophoresis mobility shift assay (EMSA). Results : Our results indicated that MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) significantly inhibited PMA/Ionomycin-induced production of IL-5 and IL-13 and the expression of IL-4, IL-5, IL-6 and IL-13 mRNA in MC/9 mast cells. Moreover, MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) inhibited PMA/Ionomycin-induced GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos protein expression and NF-${\kappa}B$ p65 DNA binding activity in MC/9 mast cells. Conclusions : In conclusion, we suspect the anti-allergenic activities of MRAL, may be related to the regulation of transcription factors GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 DNA binding assay causing inhibition of Th2 cytokines IL-5 and IL-13 in mast cells.

Suppressive Effect of CYTG on Collagen Induced Arthritis(CIA) in DBA1/J Mice (CYTG 처방이 콜라겐 유발 관절염 모델에 미치는 효과)

  • Choi, Sung-Wook;Kim, Yong-Chan;Kim, Kyoung-Shin;Kim, Byoung-Soo;Lim, Jong-Soon;Kang, Jung-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.1
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    • pp.62-69
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    • 2007
  • To evaluate effect of CYTG on inhibiting the occurrence of arthritis, we performed the experiments including production of inflammatory cytokine and immunoglobulin in collagen arthritis model. The results were obtained as fellows. CYTG group showed inhibitory effect on arthritis incidence than control group for four weeks. Arthritis index of CYTG group reduced compared with control group. In CYTG group, production of cytokines which show suppressive effect on inflammation(IL-2, COX-2) was increased and which promotes inflammation(IL-10) was decreases in spleen. In CYTG group, production of immunoglobulin (IgG-RF) was reduced compared with control, and rate of CD3+CD69+T cell is lower in lymph node and CD4+CD25+ T cell is higher in lymph node and spleen. And synovial infiltration in the knee were observed in the controls (PBS-treated mice), whereas CYTG-treated mice exhibited significantly reduced histologic evidence of destruction and inflammation. So, the histopathological scoring average of CYTG group was 2.5 compared with control group(CIA mice) 4.5. It was thought that our data express high effect via immune system specially through the controling the inflammatory cytokines and immunoglobulins. CYTG could be usefully applied for the prevention and treatment of RA, and also is expected to be clinically helpful on the treatment of RA through modification.

Immunologic Mechanism of Experimental and Therapeutic Ultraviolet B Responses

  • Lew, Wook
    • IMMUNE NETWORK
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    • v.2 no.2
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    • pp.65-71
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    • 2002
  • The immunological mechanism of the responses to ultraviolet (UV) B radiation in mouse models were investigated by the suppression of contact hypersensitivity (CHS) and delayed type hypersensitivity (DTH), and susceptibility to infection. However, there are some differences in immune suppression according to the different models as well as the irradiation protocols. Therefore, this review focused on the differences in the suppressive effects on CHS and DTH, and susceptibility to infection in relation to the different in vivo models. Recent advances in cytokine knockout mice experiments have the reexamination of the role of the critical cytokines in UVB-induced immune suppression, which was investigated previously by blocking antibodies. The characteristics of the suppressor cells responsible for UVB-induced tolerance were determined. The subcellular mechanism of UVB-induced immune suppression was also explained by the induction of apoptotic cells through the Fas and Fas-ligand interaction. The phagocytosis of the apoptotic cells is believed to induce the production of the immune suppressive cytokine like interleukin-10 by macrophages. Therefore, the therapeutic UVB response to a skin disease, such as psoriasis, by the depletion of infiltrating T cells could be considered in the extension line of apoptosis and immune suppression.

Regulation of Proopiomelanocortin and Melanocortin 1 Receptor by UVB: Inhibitory Effect of Antioxidants

  • Funasaka, Yoko
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.201-204
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    • 2002
  • Epidermal cells produce a panel of antioxidants as well as cytokines after UVB irradiation, which counteract reactive oxygen species, however, how these antioxidants might regulate melanogenesis is unclear. An important constituent of the cellular antioxidant buffering system which controls the redox state of proteins is thioredoxin (TRX), a 13-kD protein that catalyzes thiol-disulfide exchange reactions, regulates activation of transcription factors, and possesses several other biological functions similar to cytokines. TRX suppressed the UVB-induced production and secretion of $\alpha$-melanocyte stimulating hormone ($\alpha$-MSH) and of adrenocorticotropic hormone (ACTH), and also suppressed proopiomelanocortin (POMC) mRNA expression by normal human keratinocyte (KC)s. Further, L-cysteine, N-acetyl-cysteine, $\alpha$-tocopheryl ferulate showed suppressive effect on UVB-induced POMC mRNA expression. However, TRX released from UVB-irradiated KCs stimulated melanogenesis by up-regulating MSH receptor expression and its binding activity in melanocyte (MC)s. UVB-induced KC derived cytokines such as IL1, IL6, and ET1 upregulated MSH-receptor binding ability as well as MCl-R mRNA expression in cultured normal human MCs. MCl-R has a tendency to be upregulated by UVB-induced KC-derived cytokines as well as by direct UVB irradiation. These results suggest that antioxidants such as TRX suppresses UVB induction of POMC, but in the case of MCl-R, this gene can be mainly in the trend of upregulation by UVB-induced KC-derived factors including TRX.

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Altered Cell to Cell Communication, Autophagy and Mitochondrial Dysfunction in a Model of Hepatocellular Carcinoma: Potential Protective Effects of Curcumin and Stem Cell Therapy

  • Tork, Ola M;Khaleel, Eman F;Abdelmaqsoud, Omnia M
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8271-8279
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    • 2016
  • Background: Hepato-carcinogenesis is multifaceted in its molecular aspects. Among the interplaying agents are altered gap junctions, the proteasome/autophagy system, and mitochondria. The present experimental study was designed to outline the roles of these players and to investigate the tumor suppressive effects of curcumin with or without mesenchymal stem cells (MSCs) in hepatocellular carcinoma (HCC). Materials and Methods: Adult female albino rats were divided into normal controls and animals with HCC induced by diethyl-nitrosamine (DENA) and $CCl_4$. Additional groups treated after HCC induction were: Cur/HCC which received curcumin; MSCs/HCC which received MSCs; and Cur+MSCs/HCC which received both curcumin and MSCs. For all groups there were histopathological examination and assessment of gene expression of connexin43 (Cx43), ubiquitin ligase-E3 (UCP-3), the autophagy marker LC3 and coenzyme-Q10 (Mito.Q10) mRNA by real time, reverse transcription-polymerase chain reaction, along with measurement of LC3II/LC3I ratio for estimation of autophagosome formation in the rat liver tissue. In addition, the serum levels of ALT, AST and alpha fetoprotein (AFP), together with the proinflammatory cytokines $TNF{\alpha}$ and IL-6, were determined in all groups. Results: Histopathological examination of liver tissue from animals which received DENA-$CCl_4$ only revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules. Administration of curcumin, MSCs; each alone or combined into rats after induction of HCC improved the histopathological picture. This was accompanied by significant reduction in ${\alpha}$-fetoprotein together with proinflammatory cytokines and significant decrease of various liver enzymes, in addition to upregulation of Cx43, UCP-3, LC3 and Mito.Q10 mRNA. Conclusions: Improvement of Cx43 expression, nonapoptotic cell death and mitochondrial function can repress tumor growth in HCC. Administration of curcumin and/or MSCs have tumor suppressive effects as they can target these mechanisms. However, further research is still needed to verify their effectiveness.

Suppressive Effects of GST on Cytokine-induced Activation of Human Fibroblast-like Sinoviocytes (가미사물탕(GST)의 사이토카인으로 유도된 인간 섬유아세포양 활막 세포 활성화 저해 작용)

  • Park, Jee-Young;Jin, Mi-Rim;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.14 no.2
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    • pp.45-54
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    • 2005
  • GST, an extract from 16 herbs, has been formulated and prescribed for the treatment of human rheumatoid arthritis(hRA) for many years. The present study was done to investigate whether GST has suppressive effects on activation of fibroblast-like sinoviocytes isolated from an RA patient. In tumor necrosis factor-a(TNF-a)/interleukin-1b(IL-1b) treated human sinoviocytes, The mRNA expression of molecular indicators related to pathologic changes of the sinoviocytes were examined using quantitative real-time PCR. The treatment of GST($100\;{\mu}g/ml$) suppressed the expression of proinflammatory cytokines and chemokines such as TNF-a, IL-1b, IL-6 and IL-8 compared with the control. The mRNA level of intracellular adhesion molecule-1(ICAM-1) which is known to increase in the activated sinoviocytes of RA patients, was slightly decreased by GST. The expression of NOS-II was considerably reduced, which was accompanied by a decrease in the production of nitric oxide(NO). In addition, GST considerably increased the mRNA levels of tissue inhibitors of matrix metalloproteinase-1(TIMP-1), while those of matrix metalloproteinase-3(MMP-3) were decreased. Taken together, these data suggested that GST might suppress the activation of sinoviocytes in hRA.

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Suppressive Effect of SaengRyoSaMulTang on Activated RBL-2H3 Mast Cells (RBL-2H3 비만세포의 알레르기 염증 반응에 미치는 생료사물탕(生料四物湯)의 영향)

  • Son, Mi-Ju;Han, Jae-Kyung;Kim, Yun-Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.25 no.1
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    • pp.28-39
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    • 2011
  • Objectives: SaengRyoSaMulTang is a herbal formula in Oriental Medicine, known anti-allergens. However, its mechanism and cellular targets have not been found yet. Thus the study has developed to investigate the suppressive effect of SaengRyoSaMulTang. Methods: In the study, cellular viability, IL-4, IL-13 mRNA expression, IL-4, IL-13 production, manifestations of GATA-1, GATA-2, NF-AT1, NF-AT2, AP-1 and NF-${\kappa}$B p65 transcription factors were examined by Real-Time PCR, ELISA analysis and western blotting. Results: As a result of treating with SaengRyoSaMulTang extract(SRSMT), the study has shown that the amount of Th2 cytokines, which include PI induced IL-4 and IL-13, plays a significant role in suppressing effect. RBL-2H3 mast cells significantly suppressed the PI-induced Th2 cytokine production including IL-4 and IL-13 in a dose dependent manner. PI-induced IL-4 and IL-13 production was significantly suppressed by SRSMT intervention. Western blot analysis of transcription factors involving IL-4 and IL-13 expression also revealed a prominent decreases of mast cell's specific transcription factors including GATA-1, GATA-2, NF-AT2, c-Jun and c-Fos, but NF-${\kappa}$B p65. Conclusions: The study suggests that the anti-allergenic activities of SRSMT may regulate the transcription factors GATA-1, GATA-2, NF-AT2, c-Jun and c-Fos inhibiting Th2 cytokines IL-4 and IL-13 in mast cells.

Suppression of Spontaneous Dermatitis in Nc/Nga Atopic Model by Gamipaidok-san, a Traditional Herbal Medicine (가미패독산(加味敗毒散) 경구 투여에 의한 Nc/Nga 생쥐의 아토피 피부염 억제 작용)

  • Jin, Ga-Hyun;Jin, Mi-Rim;Choi, Jeung-Mok;Yun, Mi-Young;Kim, Dong-Hee
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.4
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    • pp.866-874
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    • 2006
  • Atopic dermitiis(AD) is a chronic inflammatory skin disease, which requires safe and effective medicinal therapy. Over production of Th2 cytokines and chemokines as well as IgE, which are mediated by highly activated immune cells, have been considered as pathologic factors in this disease. We found that Gamipaidok-san(GPDS), which is a traditional herbal medicine clinically prescribing for atopic dermitis patients in the hospital, has suppressive effects on the development of DNC8 induced dermatitis in Nc/Nga atopic model. Oral administration of GPDS at the concentration of 250 mg/Kg for 12 weeks significantly suppressed the clinical severity of the dermatitis including pruities, edema, eczematous and dryness. Histological examination revealed that thickness of dermis and epidermis were considerably reduced, and the number of infiltrated inflammatory immune cells including mast cells, CCR3+, and CD4+ T cells were decreased in the affected skin and ear, and consistantly, the number of CD3+/CCR3+ cells in Iymph nodes were decreased. The levels of Th2 cytokines produced by activated splenocyte from atopic mice were also down-regulated by GPDS. Furthermore, the serum levels of IgE were considerably reduced, which accompanied by a decrease in the number of B220+IgE+ B cells in the Iymph nodes. Taken together, these results suggested that oral administration of GPDS, a traditional herbal medicine, has suppressive effects on atopic dermitis of Nc/Nga mouse by the modulation of the immune system, therefore GPDS has potential as a natural therapeutic for treatment of atopic dermatitis.