• Title/Summary/Keyword: IL-9

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The Suppressive Effect of Th2 Cytokines Expression and the Signal Transduction Mechanism in MC/9 Mast Cells by Forsythiae Fructus Extracts (비만세포에서 연교(連翹) 추출물의 Th2 사이토카인 발현 및 신호전달 기전 억제 효과)

  • Lee, Jin Hwa;Han, Jae Kyung;Kim, Yun Hee
    • The Journal of Pediatrics of Korean Medicine
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    • v.28 no.3
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    • pp.31-46
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    • 2014
  • Objectives Forsythiae Fructus treatment has been used for inflammatory and allergic diseases in Korean Medicine. Nevertheless, the mechanism of action and the cellular targets are not understood well. The pathogenesis of allergic diseases are associated with Th2 cytokines such as IL-13, MIP-$1{\alpha}$, IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$ and IL-6, which are secreted by the mast cells. This study was conducted to investigate the effects of Forsythiae Fructus extracts (FF) on Th2 cytokines expression and signal transduction in MC/9 mast cells. Methods In the study, MC/9 mast cells were stimulated with DNP-IgE for 24 hours and then treated separately with CsA $10{\mu}g/m{\ell}$ and varying doses of FF for one hour. MC/9 mast cells stimulated with DNP-IgE was the control group, a treatment with CsA was the positive control group and a treatment with varying doses FF was the experimental groups. The mRNA levels of IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$, IL-6 were analyzed with Real-time PCR. The levels of IL-13, MIP-$1{\alpha}$ were measured using enzyme-linked immunosorbent assays(ELISA). NFAT, AP-1 and NF-${\kappa}B$ p65 were examined by Western blot analysis. Results 1. FF were observed to suppress the mRNA expression of IL-13, IL-5, GM-CSF, IL-4, TNF-${\alpha}$, IL-6 in comparison to DNP-IgE control group. 2. FF also has inhibited the IL-13, MIP-$1{\alpha}$ production significantly in comparison to DNP-IgE control group. 3. Western blot analysis of transduction factors involving Th2 cytokines expression has revealed a prominent decrease of the mast cell specific transduction factors including NFAT-1, NFAT-2, c-Jun, and NF-${\kappa}B$ p65 but c-Fos. Conclusions In conclusion, the anti-allergenic activities of FF may be strongly related to the regulation of transcription factors NFAT-1, NFAT-2, c-Jun, and NF-${\kappa}B$ p65 causing inhibition of Th2 cytokines in mast cells.

Anti-inflammatory effect of Equisetum hyemale via suppression of nuclear factor-κB activation in human mast cells

  • Jeon, So-Ra;Na, Ho-Jeong;Jeon, Hoon
    • Advances in Traditional Medicine
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    • v.9 no.2
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    • pp.149-156
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    • 2009
  • Equisetum hyemale Linne. (EH) (Equisetaceae) has been used for the treatment of eye and skin disease, chronic eczema, pneumoconiosis and asthma in Korea and China. Human leukemic mast cells are widely distributed in the connective tissues of mammals and other vertebrates. Phorbol 12-myristrate 13-acetate (PMA) and calcium ionophore A23187 stimulated Human leukaemic mast cell line-1 (HMC-1) can produce a variety of inflammatory mediators and several pro-inflammatory and chemotactic cytokines such as TNF-$\alpha$, IL-6 and IL-8. Since TNF-$\alpha$, IL-6 and IL-8 are major factors during the inflammatory process, we studied the effects of EH on TNF-$\alpha$, IL-6 and IL-8 release in HMC-1 stimulated with PMA and A23187. The result of this study indicate that EH inhibits TNF-$\alpha$, IL-6 and IL-8 in activated HMC-1 cells via $I{\kappa}B$/Nuclear factor-${\kappa}B$ pathway. Therefore, EH might contribute significantly to the prevention or treatment of mast-cell mediated inflammatory diseases and EH has potential use in the therapy of chronic allergic inflammation.

Immunoenhancing Effects of Conjugated Linoleic Acid on Chemotactic Activity of Porcine Peripheral Blood Polymorphonuclear Cells (돼지 말초혈액 다형핵 백혈구의 유주성에 있어서 conjugated linoleic acid의 면역증강효과)

  • Kim, Ju-hyang;Chung, Chung-soo;Lee, Chul-young;Yang, Mhan-pyo
    • Journal of Veterinary Clinics
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    • v.20 no.1
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    • pp.1-6
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    • 2003
  • Immunoenhancing effects of conjugated linoleic acid (CLA) isomers (l0t-l2c CLA, 9c-11t CLA, CLA mixture, 9c-11c CLA and 9t-11t CLA) on chemotactic activity of porcine peripheral blood polymorphonuclear cells (PMN) were examined. The chemotactic activity of PMN was evaluated by a modified Boyden chamber assay. CLA isomers at higher concentration of 50 to 200$\mu$M exhibited a low viability of cells by trypan blue exclusion. CLA isomers were used at concentration of 20uM showing no cytotoxic effect and high cell viability. CLA isomers themselves were not active or slight chemotactic for PMN. But culture supernatant from mononuclear cells (MNC) treated with 10t-12c CLA, 9c-11t CLA and CLA mixture except for 9c-11c. CLA and 9t-11t CLA enhanced remarkably chemotactic activity or porcine PMN PMN migration by culture supernatant from MNC treated with CLA mixture was found to be true chemotaxis by checkboard assay. This migration was also induced by porcine recombinant interleukin (rIL)-8. PMN chemotaxis caused both culture supernatant from MNC treated with CLA mixture and porcine rIL-8 was inhibited in a dose-dependent manner by addition of anti-porcine IL-8 polyclonal antibody. Therefore, these results strongly suggested that CLA (10t-12c CLA, 9c-11t CLA and CLA mixture) could stimulate porcine MNC to release and IL-8 like chemotactic activity.

Effect of Pulsed Electromagnetic Field on MMP-9 and TIMP-1 Levels in Chondrosarcoma Cells Stimulated with IL-1β

  • Caliskan, Serife Gokce;Bilgin, Mehmet Dincer;Kozaci, Leyla Didem
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2701-2705
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    • 2015
  • Chondrosarcoma, the second most common type of bone malignancy, is characterized by distant metastasis and local invasion. Previous studies have shown that treatment by pulsed electromagnetic field (PEMF) has beneficial effects on various cancer cells. In this study, we investigated the effects of PEMF applied for 3 and 7 days on the matrix metalloproteinase (MMP) levels in chondrosarcoma SW1353 cells stimulated with two different doses of $IL-1{\beta}$. SW1353 cells were treated with (0.5 and 5 ng/ml) $IL-1{\beta}$ and PEMF exposure was applied either 3 or 7 days. MMP-9 and TIMP-1 levels were measured in conditioned media by enzyme-linked immunosorbent assay. The results were relative to protein levels. Statistical analyses were performed using one-way analysis of variance (ANOVA). P<0.05 was considered significant. PEMF treatment significantly decreased MMP-9 protein levels in human chondrosarcoma cells stimulated with 0.5 ng/ml $IL-1{\beta}$ at day 7, whereas it did not show any effect on cells stimulated with 5 ng/ml $IL-1{\beta}$. There was no significant change in TIMP-1 protein levels either by $IL-1{\beta}$ stimulation or by PEMF treatment. The results of this study showed that PEMF treatment suppressed $IL-1{\beta}$-mediated upregulation of MMP-9 protein levels in a dual effect manner. This finding may offer new perspectives in the therapy of bone cancer.

Therapeutic Effects of Sesamum Indicum Extracts on Atopic Dermatitis-Like Skin Lesions of NC/Nga Mouce (호마자 추출물이 NC/Nga 생쥐의 아토피 피부염에 미치는 영향)

  • Kim, Yun Hee;Lee, Hye Lim
    • The Journal of Pediatrics of Korean Medicine
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    • v.29 no.4
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    • pp.39-66
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    • 2015
  • Objectives The purpose of this study is to investigate the effects of Sesamum indicum extracted (SEI) on atopic dermatitis in an in-vitro and in-vivo experiment using a MC/9 murine mast cells and a NC/Nga mouse. Methods In-vitro experiment, IL-4, IL-5, IL-6, IL-13, TNF-${\alpha}$ and GM-CSF mRNA expression were evaluated by Real-time PCR, IL-13, MIP-$1{\alpha}$ production by ELISA and manifestations of NFAT-1, NFAT-2, c-jun, c-fos, NF-${\kappa}B$ p65 transcription factors by western blotting. In-vivo experiment, we measured WBC, Eosinophil, Neutrophil, and serum IL-5, IL-13 in NC/Nga atopic dermatitis mouse, IL-5, IL-13, IFN-${\gamma}$, IL-4 in the spleenocyte culture supernatant by ELISA, the absolute cell numbers of CD4+, CD8+, +Gr-1+CD11b, B220+CD23+ in the axillary lymph node (ALN), peripheral blood mononuclear cells (PBMCs) and dorsal skin tissue, IL-5, IL-13 by Real-time PCR, the distribution of tissue inflammation and cellular infiltration by H&E and toluidine blue. Results SEI decreased IL-4, IL-5, IL-6, IL-13, GM-CSF, TNF-${\alpha}$ mRNA expression, IL-13, MIP-$1{\alpha}$ production and the expression of transcription factors including NFAT-1, c-jun, NF-${\kappa}B$ p65 in MC/9 murine mast cells. SEI orally administration decreased cell number of WBC, Eosinophil, the level of serum IgE, total cell number of ALN and dorsal skin tissue, absolute cell number of CD4+, CD8+, B220+CD23+ in the ALN. SEI orally administration also increased absolute cell number of CD8+/CD3+ and decreased Gr-1+/CD11b+ in PBMCs, decreased CD4+ in dorsal skin tissue, inhibited IL-5, IL-13 mRNA expression. Infiltration levels of inflammatory immune cells, mast cells and thickness of epidermis decreased in dorsal skin tissue. Conclusions SEI can regulate allergic inflammatory response suppressed the gene expression and production of cytokines that mediate allergic reactions, and will be able to be effectively utilized in the treatment of atopic dermatitis future.

Associations of IL-10 Gene Polymorphisms with Acute Myeloid Leukemia in Hunan, China

  • Yao, Chen-Jiao;Du, Wei;Chen, Hai-Bing;Xiao, Sheng;Wang, Cheng-Hong;Fan, Zi-Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.4
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    • pp.2439-2442
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    • 2013
  • We investigated the possible association of interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) and susceptibility to acute myeloid leukemia (AML) in 115 patients and 137 healthy controls. Genetic analysis of IL-10 SNPs at -819 and -592 was carried out with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The IL-10 mRNA expression of AML patients and controls with different genotype was detected by real-time quantitative polymerase chain reaction (RT-PCR). Genetic analysis of IL-10 revealed that the -819AA genotype frequencies and the -819A allele frequencies in the AML group were higher than in the controls (59.1% vs 40.9%; 75.6% vs 63.9%, respectively); there were remarkable differences in -819T/C and -592A/C gene distribution (P<0.05) and the TA haploid frequencies were higher in the AML group (75.6% vs 63.9%, P<0.05). IL-10 mRNA expression in incipient AML patients was obvious higher than the non-tumor group and the remission group ($7.78{\times}10^{-3}$ vs $2.43{\times}10^{-3}$, $3.64{\times}10^{-3}$, P<0.05).The study suggested that the haploid TA and genotype TA/TA may be associated with AML in Han people in Hunan province.The IL-10 SNPs at -819 and -592 sites were associated with AML and may affect IL-10 mRNA expression in AML patients.

Anti-apoptotic Effects of House Dust Mite, S100A8 and S100A9 on Spontaneous Apoptosis of Neutrophils in Coculture with Immune Cells and in the Presence of T Helper Cytokines

  • Kim, In Sik;Lee, Ji-Sook
    • Biomedical Science Letters
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    • v.21 no.2
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    • pp.122-125
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    • 2015
  • House dust mite (HDM) as a major allergen and damage-associated molecular pattern (DAMP) such as S100A8 and S100A9 trigger the pathogenesis and severity of allergic disease such as asthma. Regulation of neutrophil apoptosis is an important immune response and its dysregulation is involved in pathogenesis of allergic diseases. In this study, we examined the effects of HDM, S100A8 and S100A9 on spontaneous apoptosis of normal neutrophils. We considered the importance of the difference between in vitro and in vivo results and developed a new in vitro system consisting of a combination of immune cells and T helper (Th) cytokines. Extract of Dermatophagoides pteronyssinus (DP), S100A8, and S100A9 inhibited neutrophil apoptosis in culture of neutrophils alone without other leukocytes. DP and S100A8 more strongly suppressed neutrophil apoptosis in combinations of neutrophils, eosinophils, lymphocytes or monocytes than in a culture of neutrophils alone. Anti-apoptotic effect of S100A9 in the mixture of immune cells was similar to that in neutrophils. DP, S100A8, and S100A9 blocked neutrophil apoptosis, regardless of pretreatment with a T helper (Th) 1 cytokine (IFN-$\gamma$), Th2 cytokines (IL-4 and IL-10), a Th9 cytokine (IL-9), a Th17 cytokine (IL-17), a Treg-producing cytokine (TGF-$\beta$). These findings may enable elucidation of allergy pathogenesis due to HDM and DAMP.

Megakaryocyte-Derived IL-8 Acts as a Paracrine Factor for Prostate Cancer Aggressiveness through CXCR2 Activation and Antagonistic AR Downregulation

  • Sadan, Dahal;Prakash, Chaudhary;Yi-Sook, Jung;Jung-Ae, Kim
    • Biomolecules & Therapeutics
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    • v.31 no.2
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    • pp.210-218
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    • 2023
  • Prostate cancer is the fifth leading cause of cancer-related mortality in men, primarily because of treatment resistance, recurrence, and metastasis. In the present study, we investigated the role of paracrine interleukin-8 (IL-8) in the antagonistic expression of IL-8 and androgen receptor (AR), and the contribution of IL-8 to prostate cancer aggressiveness. In hormone-responsive LNCaP cells that do not express IL-8, recombinant IL-8 treatment significantly increased expressions of IL-8, CXC chemokine receptor 2 (CXCR2), matrix metalloproteinase (MMP)-2/9, Snail, and vimentin. IL-8 treatment significantly decreased AR and E-cadherin expression. IL-8-induced gene expression changes were suppressed by navarixin, a CXCR1/2 inhibitor, and gallein, a Gβγ inhibitor. In PC-3 androgen-refractory prostate cancer cells, IL-8 knockdown reduced expressions of CXCR2, MMP-2/9, Snail, and vimentin, and increased AR and E-cadherin expressions at the mRNA and protein levels. Co-culture with MEG-01 human megakaryocytic cells secreting high levels of IL-8 induced gene expression changes in both LNCaP and PC-3 cells, similar to those induced by IL-8 treatment. The altered gene expressions were accompanied by significant activation of transcription factor Snail in LNCaP and PC-3 cells. Treatment with the CXCR blocker navarixin inhibited the invasion of PC-3 cells but not LNCaP cells. However, invasion induced by MEG-01 was inhibited by navarixin in both LNCaP and PC-3 cells. The collective findings demonstrate that IL-8 enhances CXCR2 expression, which antagonistically regulates AR expression. More importantly, through changes in IL-8/CXCR2-regulated gene expression, IL-8 induces antiandrogen therapy resistance and epithelial-mesenchymal transition in prostate cancer.

The Effect of Substituents on LC Behavior of Bis(p-substituted phenyl) 2-Decyloxyterephthalate (Bis(p-substituted phenyl) 2-decyloxyterephthalate의 액정 특성에 대한 치환기 효과)

  • Park, Joo-Hoon;Lee, Jong-Kyu;Choi, Ok-Byung;So, Bong-Keun;Lee, Soo-Min;Lee, Jun-Woo;Jin, Jung-Il
    • Journal of the Korean Chemical Society
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    • v.44 no.2
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    • pp.127-137
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    • 2000
  • Eleven new compounds that are composed of bis(p-substituted phenyl) terephthalate unitand the decyloxy pendant as lateral were synthesized and their thermal and liquid crystalline properties were studied by the differential scanning calorimetry (DSC) and on a hot-stage of a polarizing microscope. The ter-minal substituent groups of the compound were varied; X= -H(II-H), -F(lI-F), -CII(II-CI), -Br(ll-Br), -I(II-I), -$NO_2(lI-NO_2$), $-CF_3(II-CF_3$), -$OC_2H_5(II-OC_2H_5$), -$OC_4H_9(II-OC_4H_9$), -$C_6H_5(Il-C_6H_5$). The compounds of $II-OC_2H_5,\;II-OC_4H_9$ and $II-C_6H_5$ were monotropically nematic. In contrast, the compounds of Il-H, II-F, II-Cl, II-Br, II-I, $lI-NO_2$, $II-CF_3$, and II-CN did not show liquid crystalline properties.

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