• 제목/요약/키워드: $I{\kappa}B{\alpha}$ expression

검색결과 373건 처리시간 0.026초

HaCaT 각질형성세포에서 개똥쑥(Artemisia annua L) 유래 성분인 Artemisinic acid의 Macrophage-derived Chemokine 억제 효과 (Inhibitory Effect of Artemisinic Acid Isolated from Artemisia Annua L on the MDC in HaCaT Keratinocytes)

  • 강경진;강나진;한상철;구동환;김영수;이진혁;김상철;박덕훈;이종성;강희경;유은숙
    • 생약학회지
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    • 제43권3호
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    • pp.217-223
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    • 2012
  • In the present study, we investigated anti-inflammatory activity of artemisinic acid in HaCaT cells and RAW264.7 cells. Artemisinic acid showed inhibitory activity on macrophage-derived chemokines (MDC) expression, a factor related with atopic dermatitis (AD), in interferon (IFN)-${\gamma}$ and tumor necrosis factor (TNF)-${\alpha}$-stimulated HaCaT cells. In the study on action mechanism, pretreated artemisinic acid reduced the phosphorylation of STAT1 and p38 and the degradation of $I{\kappa}B$ by IFN-${\gamma}$ and TNF-${\alpha}$ stimulations. However, artemisinic acid didn't show the inhibitory activity on LPS-induced inflammatory mediators (NO, $PGE_2$, IL-6) in RAW264.7 cell. These results indicate that artemisinic acid inhibits IFN-${\gamma}$ and TNF-${\alpha}$-induced MDC expression through inhibition of signal factors, STAT1, NF-${\kappa}B$, and p38, in HaCaT keratinocytes.

Exopolysaccharide-Overproducing Lactobacillus paracasei KB28 Induces Cytokines in Mouse Peritoneal Macrophages via Modulation of NF-${\kappa}B$ and MAPKs

  • Kang, Hee;Choi, Hye-Sun;Kim, Ji-Eun;Han, Nam-Soo
    • Journal of Microbiology and Biotechnology
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    • 제21권11호
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    • pp.1174-1178
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    • 2011
  • Exopolysaccharides (EPSs) are microbial polysaccharides that are released outside of the bacterial cell wall. There have been few studies on EPS-producing lactic acid bacteria that can enhance macrophage activity and the underlying signaling mechanism for cytokine expression. In the current study, EPS-overproducing Lactobacillus (L.) paracasei KB28 was isolated from kimchi and cultivated in conditioned media containing glucose, sucrose, and lactose. The whole bacterial cells were obtained with their EPS being attached, and the cytokine-inducing activities of these cells were investigated. Gas chromatography analysis showed the presence of glucose, galactose, mannose, xylose, arabinose, and rhamnose in EPS composition. EPS-producing L. paracasei KB28 induced the expression of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-12 in mouse macrophages. This strain also caused the degradation of $I{\kappa}B{\alpha}$ and phosphorylation of the major MAPKs: Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK)1/2. The use of pharmacological inhibitors showed that different signaling pathways were involved in the induction of TNF-${\alpha}$, IL-6 and IL-12 by L. paracasei KB28. Our results provide information for a better understanding of the molecular mechanisms of the immunomodulatory effect of food-derived EPS-producing lactic acid bacteria.

Quercetin Derivatives from Siegesbeckia glabrescens Inhibit the Expression of COX-2 Through the Suppression of NF-κB Activation in Microglia

  • Lim, Hyo-Jin;Li, Hua;Kim, Jae-Yeon;Ryu, Jae-Ha
    • Biomolecules & Therapeutics
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    • 제19권1호
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    • pp.27-32
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    • 2011
  • The activation of microglia induces the overproduction of inflammatory mediators that are responsible for the neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. The large amounts of prostaglandin $E_2$ ($PGE_2$) produced by inducible cyclooxygenase (COX-2) is one of the main inflammatory mediators that can contribute to neurodegeneration. The inhibition of COX-2 thus may provide therapeutic strategy for the treatment of neurodegenerative diseases. From the activity-guided purification of EtOAc soluble fraction of Siegesbeckia glabrescens, four compounds were isolated as inhibitors of $PGE_2$ production in LPS-activated microglia. Their structures were determined as 3, 4'-dimethylquercetin (1), 3, 7-dimethylquercetin (2), 3-methylquercetin (3) and 3, 7, 4'-trimethylquercetin (4) by the mass and NMR spectral data analysis. The compounds 1-4 showed dose-dependent inhibition of $PGE_2$ production in LPS-activated microglia with their $IC_{50}$ values of 7.1, 4.9, 4.4, $12.4\;{\mu}M$ respectively. They reduced the expression of protein and mRNA of COX-2 through the inhibition of I-${\kappa}B{\alpha}$ degradation and NF-$\kappa}B$ activity that were correlated with the inactivation of p38 and ERK. Therefore the active compounds from Siegesbeckia glabrescens may have therapeutic effects on neuro-inflammatory diseases through the inhibition of overproduction of $PGE_2$ and suppression of COX-2 overexpression.

Micronized and Heat-Treated Lactobacillus plantarum LM1004 Stimulates Host Immune Responses Via the TLR-2/MAPK/NF-κB Signalling Pathway In Vitro and In Vivo

  • Lee, Jisun;Jung, Ilseon;Choi, Ji Won;Lee, Chang Won;Cho, Sarang;Choi, Tae Gyu;Sohn, Minn;Park, Yong Il
    • Journal of Microbiology and Biotechnology
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    • 제29권5호
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    • pp.704-712
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    • 2019
  • Although nanometric dead Lactobacillus plantarum has emerged as a potentially important modulator of immune responses, its underlying mechanism of action has not been fully understood. This study aimed to identify the detailed biochemical mechanism of immune modulation by micronized and heat-treated L. plantarum LM1004 (MHT-LM1004, <$1{\mu}m$ in size). MHT-LM1004 was prepared from L. plantarum LM1004 via culture in a specifically designed membrane bioreactor and heat treatment. MHT-LM1004 was shown to effectively induce the secretion of $TNF-{\alpha}$ and IL-6 and the mRNA expression of inducible nitric oxide synthase (iNOS). MHT-LM1004 enhanced the expression of TLR-2, phosphorylation of MAPKs (ERK), and nuclear translocation of $NF-{\kappa}B$ in a dose-dependent manner. Oral administration of MHT-LM1004 ($4{\times}10^9$ or $4{\times}10^{11}cells/kg$ mouse body weight) increased the splenocyte proliferation and serum cytokine levels. These results suggested that MHT-LM1004 effectively enhances early innate immunity by activating macrophages via the TLR-2/MAPK/$NF-{\kappa}B$ signalling pathway and that this pathway is one of the major routes in immune modulation by the Lactobacillus species.

Scrophularia Buergeriana inhibits the Production of NO through the Suppression of NF-kB adivity in LPS-stimulated Mouse Peritoneal Macrophages

  • Ha Mi Suk;Kim Young Hee;Ko Woo Shin;Kim Han Do
    • 동의생리병리학회지
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    • 제16권6호
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    • pp.1284-1290
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    • 2002
  • Scrophularia buergeriana Miquel (Scrophulariaceae) has been used as an anti-inflammatory drug in the folk medicine recipe and been proved its anti-inflammatory effect in the oriental medicine. Since nitric oxide (NO) and superoxide anion (O/sub 2//sup -/) are ones of the major inflammatory parameters, we studied the effect of aqueous extracts of Scrophularia buergeriana (SB) on NO and O/sub 2//sup -/ production in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages. NO, O/sub 2//sup -/production and inducible NO synthase (iNOS) level were significantly reduced in LPS-activated macrophages by SB compared to those without. Electrophoretic mobility shift assay (EMSA) indicated that SB blocked the activation of NF-kB, which was considered to be a potential transcription factor for the iNOS expression. SB also blocked degradation of IkBα. Furthermore, IkB kinase alpha (IKKα), which phosphorylates serine residues of IkB directly, is inhibited by SB. These results suggest that SB could exert its anti-inflammatory actions by suppressing the activation of NF-kB through inhibition of IKK activity.

Resveratrol raises in vitro anticancer effects of paclitaxel in NSCLC cell line A549 through COX-2 expression

  • Kong, Fanhua;Zhang, Runqi;Zhao, Xudong;Zheng, Guanlin;Wang, Zhou;Wang, Peng
    • The Korean Journal of Physiology and Pharmacology
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    • 제21권5호
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    • pp.465-474
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    • 2017
  • The aim of this study was to determine the raising anticancer effects of resveratrol (Res) on paclitaxel (PA) in non-small cell lung cancer (NSCLC) cell line A549. The $10{\mu}g/ml$ of Res had no effect on human fetal lung fibroblast MRC-5 cells or on A549 cancer cells and the 5 or $10{\mu}g/ml$ of PA also had no effect on MRC-5 normal cells. PA-L ($5{\mu}g/ml$) and PA-H ($10{\mu}g/ml$) had the growth inhibitory effects in NSCLC cell line A549, and Res increased these growth inhibitory effects. By flow cytometry experiment, after Res ($5{\mu}g/ml$)+PA-H ($10{\mu}g/ml$) treatment, the A549 cells showed the most apoptosic cells compared to other group treatments, and after additional treatment with Res, the apoptosic cells of both two PA concentrations were raised. Res+PA could reduce the mRNA and protein expressions of COX-2, and Res+PA could reduce the COX-2 related genes of VEGF, MMP-1, MMP-2, MMP-9, $NF-{\kappa}B$, Bcl-2, BclxL, procollagen I, collagen I, collagen III and CTGF, $TNF-{\alpha}$, $IL-1{\beta}$, iNOS and raise the TIMP-1, TIMP-2, TIMP-3, $I{\kappa}B-{\alpha}$, p53, p21, caspase-3, caspase-8, caspase-9, Bax genes compared to the control cells and the PA treated cells. From these results, it can be suggested that Res could raise the anticancer effects of PA in A549 cells, thus Res might be used as a good sensitizing agent for PA.

Lactic Acid Bacteria Isolated from Human Breast Milk Improve Colitis Induced by 2,4,6-Trinitrobenzene Sulfonic Acid by Inhibiting NF-κB Signaling in Mice

  • Kyung-Joo Kim;Suhyun Kyung;Hui Jin;Minju Im;Jae-won Kim;Hyun Su Kim;Se-Eun Jang
    • Journal of Microbiology and Biotechnology
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    • 제33권8호
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    • pp.1057-1065
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    • 2023
  • Inflammatory bowel disease (IBD), a chronic inflammatory disease, results from dysregulation of the immune responses. Some lactic acid bacteria (LAB), including Lactobacillus, alleviate IBD through immunomodulation. In this study, the anti-colitis effect of LAB isolated from human breast milk was investigated in a mouse model induced acute colitis with 2,4,6-trinitrobenzene sulfonic acid (TNBS). TNBS remarkably increased weight loss, colon shortening, and colonic mucosal proliferation, as well as the expression levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β. Oral administration of LAB isolated from human breast milk resulted in a reduction in TNBS-induced colon shortening, as well as induced cyclooxygenase (COX)-2, nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB). In addition, LAB suppressed inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and thus showed an effect of suppressing the level of inflammation induced by TNBS. Furthermore, LAB alleviated gut microbiota dysbiosis, and inhibited intestinal permeability by increasing the expression of intestinal tight junction protein including ZO-1. Collectively, these results suggest that LAB isolated from human breast milk can be used as a functional food for colitis treatment by regulating NF-κB signaling, gut microbiota and increasing expression of intestinal tight junction protein.

가미미후등식장탕이 DNCB 유도 아토피 피부염 동물모델에 미치는 효과 (Effects of KMS on the DNCB induced animal Model of Atopic Dermartitis)

  • 송대욱;민가율;홍수연;임서은;허정;손영주;정혁상
    • 대한한의학회지
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    • 제40권1호
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    • pp.63-77
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    • 2019
  • Objectives: The purpose of this study is to examine the effect of water and fermentation extracts of KMS (Kami-Mihudeongsikjang-tang) on AD (atopic dermatitis). Additionally, by applying the fermentation extracts of KMS at the first sensitization and latency period, I investgated whether it could prevent AD. Methods: In this study, to test the effect and preventive efficacy of KMSs on AD. DNCB-induced BALB/c mice of AD model was used. Through histological observation, epidermis and dermis thickness, the infiltration of eoshiphils and mast cells in epidermis and dermis were examined. We measured the serum level of IgE and IL-6, TNF-alpha, and the expressions of $NF-{\kappa}B$ and MAPK protein. In order to examine the effect of KMSs on keratinocyte, HaCaT cells were treated TNF-alpha and IFN-gamma to induce an inflammatory response. The KMSs were applied at various concentration in the experimental group. We investigated TARC expression. Results: The treatment groups were reduced epidermis and dermis thickness, inhibited the infiltration of eosinophils and mast cells, reduced the serum level of IL-6. Moreover, sfKMS group reduced serum level of TNF-alpha, inhibited the protein expressions of $NF-{\kappa}B$ and the phosphoryllation of ERK, JNK and p38. Especially sfKMS-pre group were reduced the serum level of IgE, show significant inhibition on the protein expression of $NF-{\kappa}B$ and the phosphoryllation of ERK, JNK and p38. In the experiment on HaCaT cells, sfKMS group were reduced expression of TARC. Conclusions: These result suggest that wKMS and sfKMS was effective in the treament on AD, and sfKMS would prevent AD.

Immune Enhancement Effect of Asterias amurensis Fatty Acids through NF-κB and MAPK Pathways on RAW 264.7 Cells

  • Monmai, Chaiwat;Go, Seok Hyeon;Shin, Il-shik;You, SangGuan;Lee, Hyungjae;Kang, SeokBeom;Park, Woo Jung
    • Journal of Microbiology and Biotechnology
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    • 제28권3호
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    • pp.349-356
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    • 2018
  • Asterias amurensis is a marine organism that causes damage to the fishing industry worldwide; however, it has been considered a promising source of functional components. The present study aimed to investigate the immune-enhancing effects of fatty acids from three organs of A. amurensis on murine macrophages (RAW 264.7 cells). A. amurensis fatty acids boosted production of immune-associated factors such as nitric oxide (NO) and prostaglandin E2 in RAW 264.7 cells. A. amurensis fatty acids also enhanced the expression of critical immune-associated genes, including iNOS, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6, as well as COX-2. Western blotting showed that A. amurensis fatty acids stimulated the $NF-{\kappa}B$ and MAPK pathways by phosphorylation of $NF-{\kappa}B$ p-65, p38, ERK1/2, and JNK. A. amurensis fatty acids from different tissues resulted in different levels of $NF-{\kappa}B$ and MAPK phosphorylation in RAW 264.7 cells. The results increase our understanding of how A. amurensis fatty acids boost immunity in a physiological system, as a potential functional material.

A Medium-Chain Fatty Acid, Capric Acid, Inhibits RANKL-Induced Osteoclast Differentiation via the Suppression of NF-κB Signaling and Blocks Cytoskeletal Organization and Survival in Mature Osteoclasts

  • Kim, Hyun-Ju;Yoon, Hye-Jin;Kim, Shin-Yoon;Yoon, Young-Ran
    • Molecules and Cells
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    • 제37권8호
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    • pp.598-604
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    • 2014
  • Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-${\kappa}B$ ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced $I{\kappa}B{\alpha}$ phosphorylation, p65 nuclear translocation, and NF-${\kappa}B$ transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.