• Title/Summary/Keyword: IL-6 and IL-10

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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.

Immunomodulatory effects of chlorogenic acid and ethyl acetate fraction from Lonicera japonica on cytokine gene expression profiles in spleen and thymus (Chlorogenic acid 및 인동등 ethyl acetate 분획의 비장 및 흉선 세포에서의 유전자 발현 분석을 통한 면역조절효과)

  • Ha, Tae-Kwang;Lee, Young-Cheol
    • The Korea Journal of Herbology
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    • v.26 no.2
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    • pp.1-10
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    • 2011
  • Objective : Lonicera japonica contains anti complementary polysaccharides and polyphenolic compound. Among these polyphenolic substances, chlorogenic acid is the major active component of this plant. However, the immunological mechanisms for these activities, have not been elucidated, nor the active components. To clarify immunomodulatory effects of those we examined the relationship between the activity of CD8+ T cell-mediated lysis and the frequency of cytokine profiles in spleen, thymus (especially IFN-${\gamma}$, IL-4, GM-CSF etc.) expressing CD8+ T cells activated by IL-2. Methods : To study immunomodulatory effects ethyl acetate fraction from Lonicera japonica, chlorogenic acid on cytokine gene expression from spleen, thymus cells, RT-PCR was performed after quantitative normalization for each gene by a densitometry using ${\beta}$-actin gene expression. A modified standard $^{51}Cr$-release assay was used to measure cytotoxic activities of cytotoxic T cells. Spleen, thymus cells from NOD mice were stained with CD3, CD4, CD44, CD69 in staining buffer and analyzed by two color flow cytometry. Results : We showed that ethyl acetate fraction from Lonicera japonica in combination with IL-2 resulted in a significant enhancement of PCR products for IFN-${\gamma}$, IL-4, IL-10, GM-CSF, IL-6 and cytotoxtic CD8+ T cell proportion in spleen and thymus T cells in NOD mice. This suggests that IFN-${\gamma}$, IL-6 like IL-4 may be acting as a regulatory rather than proinflammatory cytokine. Conclusions : In conclusion, based on the results of the present study which showed that ethyl acetate fraction from Lonicera japonica and chlorogenic acid upregulating cytokine gene expression in spleen and thymus, we are tempted to speculate that some of the therapeutic efficacies such as anti-diabetic activity of Lonicera japonica are due to the immunomodulatory its ethylacetate fraction and chlorogenic acid.

Effect of Therapeutic Hypercapnia on Systemic Inflammatory Responses in Hemorrhagic Shock in Rats (랫드의 출혈성 쇼크 모델에서 치료적 고탄산혈증이 전신적 염증 반응에 미치는 영향)

  • Kang, Kyeong Won;Jo, You Hwan;Kim, Kyuseok;Lee, Jae Hyuk;Rhee, Joong Eui
    • Journal of Trauma and Injury
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    • v.25 no.1
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    • pp.17-24
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    • 2012
  • Purpose: This study was performed to investigate whether therapeutic hypercapnia could attenuate systemic inflammatory responses in hemorrhagic shock in rats. Methods: Male Sprague-Dawley rats were mechanically ventilated and underwent pressure-controlled (mean arterial pressure: $38{\pm}1$ mmHg) hemorrhagic shock. At 10 minutes after the induction of hemorrhagic shock, the rats were divided into the normocapnia ($PaCO_2$=35-45 mmHg, n=10) and the hypercapnia ($PaCO_2$=60-70 mmHg) groups. The $PaCO_2$ concentration was adjusted by using the concentration of inhaled $CO_2$ gas. After 90 minutes of hemorrhagic shock, rats were resuscitated with shed blood for 10 minutes and were observed for 2 hours. The mean arterial pressure (MAP) and the heart rate were monitored continuously, and the results of arterial blood gas analyses, as well as the plasma concentrations of interleukin (IL)-6, IL-10, and nitrite/nitrate were compared between the normocapnia and the hypercapnia groups. Results: The MAP and the heart rate were not different between the two groups. The plasma concentration of IL-6 was significantly lower in the hypercapnia group than in the normocapnia group (p<0.05). The IL-10 concentration was not different and the IL-6 to IL-10 ratio was significantly lower in the hypercapnia group compared to the normocapnia group. The plasma nitrite/nitrate concentration of the hypercapnia group was lower than that of the normocapnia group. Conclusion: Therapeutic hypercapnia attenuates systemic inflammatory responses in hemorrhagic shock.

Kyungheechunggan-tang suppresses inflammatory cytokines and fibrotic genes in LPS-induced RAW 264.7 cells and LX-2 cells

  • Bae, Junghan;Jang, Eungyeong;Lee, Jang-Hoon
    • The Journal of Korean Medicine
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    • v.39 no.4
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    • pp.40-50
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    • 2018
  • Objectives: The aim of this study is to investigate anti-inflammatory effects of Kyungheechunggan-tang (KHCGT) on LPS- induced RAW 264.7 cells and LX-2 cells and anti-fibrotic effects of KHCGT on LX-2 cells. Materials and Methods: Three types of KHCGTs (KHCGT-A, -B, and -C) by narrowing down the number of constituent herbs from 9 (KHCGT-A) to 5 (KHCGT-B) and to 3 (KHCGT-C) were developed. To understand pharmacological effects of KHCGT, three types of KHCGTs were treated on RAW 264.7 cells and LX-2 cells. Anti-inflammatory activities of KHCGT were evaluated by ELISA assay for pro-inflammatory cytokines, IL-6, $TNF-{\alpha}$ and IL-10, in LPS-stimulated RAW 264.7 cells and for IL-6 production in LPS-induced LX-2 cells. In addition, anti-fibrotic effects of KHCGT were determined by quantitative real-time PCR assay for fibrosis-related genes, ${\alpha}-SMA$, collagen1A1, TIMP1, MMP-2, in LX-2 cells. Results: KHCGT-A and KHCGT-C showed inhibitory effects on secretion of IL-6 in LPS-stimulated RAW 264.7 cells and LX-2 cells. KHCGT-B and KHCGT-C exhibited inhibitory effects on the expression of pro-inflammatory cytokines such as IL-6, $TNF-{\alpha}$, and IL-10 in LPS-stimulated RAW 264.7 cells. The mRNA expression levels of collagen1A1 and MMP-2 were significantly reduced by KHCGT-C whereas TIMP-1 was suppressed by KHCGT-A and KHCGT-B in LX-2 cells. Among three different formulas, KHCGT-C demonstrated the most remarkable effects on inflammation and fibrosis. Conclusions: In this study, KHCGT showed both anti-inflammatory and anti-fibrotic effects which make it to be a prospective agent for chronic liver diseases with inflammation and fibrosis.

Mitigation effects of red Platycodon grandiflorum extract on lipopolysaccharide-induced inflammation in splenocytes isolated from mice (홍도라지 추출물이 마우스에서 분리한 비장세포에서 lipopolysaccharide로 유도된 염증에 미치는 영향)

  • Park, Eun-Jung;Lee, You-Suk;Jeong, Hyun Cheol;Lee, Sung-Hyen;Lee, Hae-Jeung
    • Journal of Nutrition and Health
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    • v.52 no.3
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    • pp.243-249
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    • 2019
  • Purpose: Platycodon grandiflorum (PG) is known to have effective antimicrobial and anticancer activity. The main bioactive components of PG are saponins, and these could contribute to anti-inflammatory activity. However, little is known about the anti-inflammatory effect of PG. In this study, we aim to assess the anti-inflammatory response to Red PG Extract (RPGE) in splenocytes under ex vivo conditions. Methods: The cell viability of isolated splenocytes taken from mice was analyzed by performing a Cell Counting Kit-8 assay. The productions of nitric oxide (NO) and cytokines (specifically interleukin-6 (IL-6) and interleukin-10 (IL-10)) were measured utilizing Griess reagent and ELISA, respectively. Results: We found that co-treatment with RPGE and Lipopolysaccharide (LPS) decreased isolated splenocyte proliferation as compared with that of the LPS-stimulated control. We also observed that RPGE markedly suppressed NO synthesis and IL-6 production that was induced by LPS. There were no significant differences of IL-10 production between co-treatment with RPGE plus LPS and treatment with LPS alone. Conclusion: When taken together, our data has shown that RPGE mitigates LPS-induced inflammation in splenocytes isolated from mice. Further research is surely needed to confirm the anti-inflammation effects of RPGE in an in vivo model.

Effects of Substance P on the Cell Proliferation and IL-2 Production of T Lymphocyte (Substance P가 T 임파구의 세포증식과 IL-2 생산에 미치는 영향)

  • Moon, Jin-Kyun;Choi, Byung-Son;Lee, Seok-Cho;Kim, Hyung-Seop
    • Journal of Periodontal and Implant Science
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    • v.27 no.4
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    • pp.805-818
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    • 1997
  • Immune responses of periodontal tissue may be regulated by products of sensory afferent nerve endings such as neuropeptides. Substance P(SP), a tachykinin neuropeptide, has been previously reported to stimulate the activities of T lymphocyte. Therefore, I examined the role of SP in IL-2 production and cell proliferation by using a homogeneous line of T lymphocytes(Jurkat and HuT78). Cell proliferation rate was determined by [$^3H$]-thymidine incorporation test, and IL-2 was quantitated by the growth rate of CD4+ IL-2-dependent T lymphocyte line CTLL-2. SP stimulated cell proliferation of T lymphocytes at the concentration of $10^{-12}$ and $10^{-8}$M in a biphasic bell-shape dose-dependent manner. However, SP alone did not induce IL-2 release at the concentration range of $10^{-6}$ to $10^{-14}$M. The upregulation of IL-2 release was observed when $10^{-12}$M SP was applied together with mitogens such as Con A or PHA+PMA on T cell lines, especially on Jurkat. Con A or PHA+PMA demonstrated to increase the rate of cell proliferation of Jurkat, which had shown to produce much amount of IL-2 indicating that mitogen-induced cell proliferation might be partially influenced by released IL-2. It was concluded that regulatory effects of SP on the immune/inflammatory response could be mediated through the costimulatory upregulation of IL-2 production and increase of cell proliferation of T lymphocyte.

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Effect of Tuna Extracts on Production of Nitric Oxide and Inflammatory Cytokines (참치 추출물의 일산화질소 및 사이토카인 생성에 미치는 영향)

  • Kim, Kwang-Hyuk;Choi, Myoung Won;Choi, Hyang Mi;Lim, Sun-Young
    • Korean Journal of Food Science and Technology
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    • v.45 no.3
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    • pp.385-390
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    • 2013
  • The effect of tuna extracts on the production of nitric oxide (NO) and cytokines including interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was investigated. All extracts and fractions from tuna significantly reduced NO production induced by lipopolysaccharide (LPS). The acetone+methylene chloride (A+M) extract, n-hexane and 85% aqueous methanol (MeOH) fractions had stronger inhibitory effects among them. The 85% aqueous MeOH fraction at a 10-${\mu}g$ concentration significantly decreased LPS-induced IL-6 and TNF-${\alpha}$ productions at 6 h of incubation. In the case of LPS-induced IFN-${\gamma}$ production, the 85% aqueous MeOH fraction at a 3-${\mu}g$ concentration showed significantly higher levels at 48 h of incubation. These results show that the 85% aqueous MeOH fraction inhibited the production of NO and pro-inflammatory cytokines (IL-6, TNF-${\alpha}$), suggesting that this fraction acts as a potent immunomodulator.

Effects of Kaempferol on Lippolysaccharide-induced Inflammation in Mouse Brain (Kaempferol이 LPS로 유도된 생쥐 중추신경계 염증에 미치는 영향)

  • Lee, Hung-Gi;Kim, Do-Hoon;Kim, Youn-Sub
    • The Korea Journal of Herbology
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    • v.30 no.1
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    • pp.77-84
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    • 2015
  • Objectives : Brain inflammation early activates the microglia and activated microglia secrete a variety of pro-inflammatory cytokines. Kaempferol, which is a flavonoid in Cuscutae Semen, shows a wide range of physiological activities, including neurons protection and anti-inflammatory actions through inhibition of pro-inflammatory mediators. The present study examined the modulatory effect of kaempferol on cytokines [tumor necrosis factor- alpha ($TNF-{\alpha}$), interleukin-1beta ($IL-1{\beta}$) and interleukin-6 (IL-6)] and cyclooxygenase-2 (COX-2) mRNA expression and microglia activation in the brain tissue of the mouse. Methods : Kaempferol was administered orally three doses of 10, 20 and 30 mg/kg respectively, once 1 hour before the lippolysaccharide(LPS) (3 mg/kg, i.p.) injection. Brain tissue was removed at 4 hours after LPS injection. Cytokines and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction (PCR) method. Iba1 expression was calculated by western blotting method. Microglia was observed with immunohistochemistry. Immunohistochemistry stained microglia was analyzed by using ImageJ software. Results : Kaempferol 20 and 30 mg/kg was significantly attenuated the expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA. Kaempfrol 10, 20 and 30 mg/kg significantly attenuated COX-2 mRNA expression in the brain tissue. Kaempferol 30 mg/kg significantly suppressed the increase of Iba1 protein expression by LPS. Kaempferol 30 mg/kg significantly decreased the number of microglia in the cerebral cortex and the number and cell size of microglia in the hypothalamic region and the area percentage of ionized calcium binding adaptor molecule 1(Iba1)-expressed microglia in the hippocampus. Conclusions : This results indicate that kaempferol plays an anti-inflammatory role in the brain.

Modulation of Th1/Th2 Cytokine Secretion in Human Peripheral Blood Mononuclear Cells by Water Extract of Acanthopanax divaricatus var. albeofructus Fruits (사람 말초혈액 단핵세포에서 흰털오가피 열매 추출물에 의한 Th1/Th2 Cytokine 분비조절)

  • Lyu, Su-Yun;Noh, Bin-Na;Park, Won-Bong
    • YAKHAK HOEJI
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    • v.52 no.1
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    • pp.27-32
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    • 2008
  • Water extracts of Acanthopanax divaricatus var. albeofructus (ADA) fruits were used to treat hPBMC to determine the mechanisms for the immunomodulatory effects. The secretion level of various cytokines including Th-1 type (IL-2, L-12, $IFN-{\gamma}$ and $TNF-{\alpha}$) and Th-2 type (IL-6, IL-8 and IL-10) were measured using ELISA. A significant increase of Th-1 type cytokine secretion was observed in the presence of extract while Th-2 cytokine, IL-6 was suppressed. Our results suggest that ADA fruit extract may influence the anticancer immune responses towards a predominance of Th-1 cytokines in the immune system.

Effects of Gossypetin from Hibiscus sabdariffa on Interleukin-6 Production in Porphyromonas gingivalis Lipopolysaccharide-Stimulated Human Gingival Fibroblasts

  • Ke Huang;Ki-Rim Kim
    • Journal of dental hygiene science
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    • v.23 no.4
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    • pp.296-301
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    • 2023
  • Background: Periodontal disease is a major cause of tooth loss in adults and is a representative oral disease commonly suffered by most people around the world. Mainly the proliferation of Gram-negative bacteria and secreted virulence factors cause an inflammatory response and destroy periodontal tissue. Gossypetin, isolated from Hibiscus sabdariffa L, is known to have various pharmacological effects, including antibacterial and anticancer activities. We aimed to confirm the anti-inflammatory effect of gossypetin through interleukin-6 (IL-6) regulation in human gingival fibroblasts (HGFs) stimulated with lipopolysaccharide (LPS) of Porphyromonas gingivalis, a major cause of adult periodontitis. Methods: CCK-8 assay was performed to confirm the concentration-dependent cytotoxicity of gossypetin against HGFs. The secretion level and mRNA expression of IL-6, an inflammation-related cytokine, and the effect of gossypetin on these in HGFs stimulated with P. gingivalis LPS were confirmed by ELISA and qRT-PCR analysis, respectively. Results: Up to a concentration of 100 µM gossypetin with or without P. gingivalis LPS, the survival rate for HGFs was maintained at over 95% and showed no toxicity. ELISA and qRT-PCR analysis results showed that P. gingivalis LPS increased IL-6 secretion and mRNA levels in HGFs compared to the control group. However, this increase in IL-6 was significantly down-regulated by gossypetin treatment in a dose-dependent manner. In particular, 80 µM gossypetin inhibited IL-6 production to the level of the control group. Conclusion: These results indicated that gossypetin attenuated IL-6 production in HGFs stimulated by P. gingivalis LPS, which may ultimately suppress the inflammatory response in periodontal tissue. Therefore, gossypetin may have potential as a natural ingredient for the prevention and treatment of periodontal disease.