• 대한한방내과학회지
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• 제28권3호
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• pp.442-452
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• 2007

Objectives : The purpose of this study was to investigate the toll-like receptor (TLR)-4 mediated anti-inflammatory effects of extract from Shigyungbanha-tang (SBT) on the peritoneal macrophage. Methods : To evaluate of TLR-4 mediated inflammatory of SBT. we examined NO and cytokine production in TRL-4 ligand (LPS : lipopolysaccharide) induced macrophages. Furthermore, we examined its molecular mechanism using western blot. Results : Extract from SBT itself does not have any cytotoxic effect in the peritoneal macrophages. Extract from SBT reduced LPS-induced nitric oxide (NO). tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin (IL)-6 and IL-12 production in peritoneal macrophages. SBT inhibited degradation of inhibitor kappa B-alpha ($I{\kappa}B-{\alpha}$) in the TLR-4 mediated peritoneal macrophages. Conclusions : These results suggest that SBT inhibits NO and cytokines production through inhibiting nuclear factor-kappaB (NF-${\kappa}$B) activation in peritoneal macrophage and that SBT may be beneficial oriental medicine for inflammation.

• Journal of Microbiology and Biotechnology
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• 제32권6호
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• pp.709-717
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• 2022

Allergic rhinitis (AR), one of the most common inflammatory diseases, is caused by immunoglobulin E (IgE)-mediated reactions against inhaled allergens. AR involves mucosal inflammation driven by type 2 helper T (Th2) cells. Previously, it was shown that the Streptococcus pneumoniae pep27 mutant (Δpep27) could prevent and treat allergic asthma by reducing Th2 responses. However, the underlying mechanism of Δpep27 immunization in AR remains undetermined. Here, we investigated the role of Δpep27 immunization in the development and progression of AR and elucidated potential mechanisms. In an ovalbumin (OVA)-induced AR mice model, Δpep27 alleviated allergic symptoms (frequency of sneezing and rubbing) and reduced TLR2 and TLR4 expression, Th2 cytokines, and eosinophil infiltration in the nasal mucosa. Mechanistically, Δpep27 reduced the activation of the NLRP3 inflammasome in the nasal mucosa by down-regulating the Toll-like receptor signaling pathway. In conclusion, Δpep27 seems to alleviate TLR signaling and NLRP3 inflammasome activation to subsequently prevent AR.

• 생명과학회지
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• 제28권12호
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• pp.1406-1415
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• 2018

본 연구는 어성초(Houttuynia cordata Thunb)의 메탄올 추출에 의한 유기 용매별 분획물에서 항산화 효과를 근거로 산화적 스트레스에 의한 HaCaT 세포보호 효과를 확인하였다. 용매별 분획물의 항산화 활성은 시료의 농도가 증가할수록 DPPH에 대한 전자공여능도 증가하였으며, $ED_{50}$은 ethyl acetate (EtOAc) 분획물에서 $175{\mu}g/ml$로 가장 높게 나타났다. $H_2O_2$에 의해 유도된 HaCaT 세포의 세포사멸($IC_{50}$)에 대하여 Hc-EtOAc 분획물은 농도 의존적으로 유의적인 세포 생존율과, $100{\mu}g/ml$ 농도에서 74%의 세포보호 효과를 나타내었다. 한편 $100{\mu}g/ml$의 Hc-EtOAc 분획물을 6 및 24시간 동안 HaCaT 세포에 처리하여 유전자 발현 양상을 분석하였다. 2 배 이상 발현이 증가된 유전자들은 신호전달, 세포분열, 항산화 활성, 상피세포 증식 등에 작용하는 것으로 나타났다. 특히 항산화 활성에 관여할 것으로 추정되는 유전자는 전염증성 사이토카인인 IL1B, TNF, 그리고 IL6 등 이었으며, 이들 유전자의 상위 조절자로써 TLR4가 확인되었다. IL1B, TNF, 그리고 IL6 유전자의 활성을 검증하기 위하여 qRT-PCR을 수행한 결과, $100{\mu}g/ml$ 이상의 Hc-EtOAc 분획물 처리군에서 2 배 이상 발현이 증가한 것으로 나타났다. 상위 조절자 TLR4 단백질의 활성 역시 Hc-EtOAc 분획물에 의해 증가되었다. 이상의 결과, Hc-EtOAc 분획물에 의한 항산화 활성은 TLR4로부터 IL1B, TNF, IL6과 같은 사이토카인을 경유하는 것으로 예측된다.

• 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.

• 농업과학연구
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• 제48권2호
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• pp.251-264
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• 2021

Bovine respiratory syncytial virus (BRSV) and bovine viral diarrhea virus (BVDV) are the main viral contributors to bovine respiratory disease (BRD) with high mortality and morbidity. BRD control measures include vaccination that modulates immunological profiles reflected in blood cells, serum, and body secretions, such as milk. This study evaluated the immune responses to an inactivated BRD vaccine in lactating cows reared in a natural environment on a dairy farm. The cows were intramuscularly inoculated with the vaccine, and serum, blood, and milk were collected pre-and post-vaccination. Our study revealed a prominent increase in BRSV-specific antibodies both in serum and milk, while the change in BVDV-specific antibodies was insignificant. Serum interleukin (IL)-1β and IL-6 levels significantly decreased, but this change was not reflected in milk. Evaluation of pattern recognition receptors (PRRs) via RT-qPCR revealed downregulation of nucleotide-binding oligomerization domain 2 (NOD2). The concentrations of BRSV antibodies, BVDV antibodies, IL-2, and IL-17A in serum and milk were strongly correlated, implying a concurrent influence on both body fluids. Thus, immunological factors modulated as a result of vaccination generally measured in serum were reflected in milk, demonstrating the suitability of milk evaluation as an alternative approach for immunological observations. Furthermore, the correlation between BRSV antibodies and NOD2 and that between BVDV antibodies and toll-like receptor (TLR) 2, TLR3, TLR4, and TLR5 imply the possible role of PRRs for the assessment of the immune response developed in immunized cows reared on the farm.

• Nutrition Research and Practice
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• 제7권6호
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• pp.460-465
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• 2013

The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/$10{\mu}g/kg$ body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.

• Journal of Microbiology and Biotechnology
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• 제19권6호
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• pp.616-621
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• 2009

To evaluate the effects of lactic acid bacteria (LAB) in inflammatory bowel diseases (IBD), we measured the inhibitory effect of several LAB isolated from intestinal microflora and commercial probiotics against the glycosaminoglycan (GAG) degradation by intestinal bacteria. Bifidobacterium longum HY8004 and Lactobacillus plantarum AK8-4 exhibited the most potent inhibition. These LAB inhibited colon shortening and myeloperoxidase production in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitic mice. These LAB also blocked the expression of the proinflammatory cytokines, IL-$1{\beta}$ and TNF-$\alpha$, as well as of COX-2, in the colon. LAB also blocked activation of the transcription factor, NF-${\kappa}B$, and expression of TLR-4 induced by TNBS. In addition, LAB reduced the TNBS-induced bacterial degradation activities of chondroitin sulfate and hyaluronic acid. These findings suggest that GAG degradation-inhibitory LAB may improve colitis by inhibiting inflammatory cytokine expression via TLR-4-linked NF-${\kappa}B$ activation and by inhibiting intestinal bacterial GAG degradation.

• Nutrition Research and Practice
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• 제15권5호
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• pp.591-603
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• 2021

BACKGROUND/OBJECTIVES: Unregulated inflammatory responses caused by hyperglycemia may induce diabetes complications. Hesperetin, a bioflavonoid, is a glycoside in citrus fruits and is known to have antioxidant and anticarcinogenic properties. However, the effect of inflammation on the diabetic environment has not been reported to date. In this study, we investigated the effect of hesperetin on proinflammatory cytokine secretion and its underlying mechanistic regulation in THP-1 macrophages with co-treatment LPS and hyperglycemic conditions. MATERIALS/METHODS: THP-1 cells differentiated by PMA (1 µM) were cultured for 48 h in the presence or absence of hesperetin under normoglycemic (5.5 mM/L glucose) or hyperglycemic (25 mM/L glucose) conditions and then treated with LPS (100 ng/mL) for 6 h before harvesting. Inflammation-related proteins and mRNA levels were evaluated by enzyme-linked immunosorbent assay, western blot, and quantitative polymerase chain reaction analyses. RESULTS: Hesperetin (0-100 µM, 48 h) treatment did not affect cell viability. The tumor necrosis factor-α and interleukin-6 levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions, and these increases were decreased by hesperetin treatment. The TLR2/4 and MyD88 activity levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions; however, hesperetin treatment inhibited the TLR2/4 and MyD88 activity increases. In addition, nuclear factor-κB (NF-κB) and Acetyl-NF-κB levels increased in response to treatment with LPS under hyperglycemic conditions compared to normoglycemic conditions, but those levels were decreased when treated with hesperetin. SIRT3 and SIRT6 expressions were increased by hesperetin treatment. CONCLUSIONS: Our results suggest that hesperetin may be a potential agent for suppressing inflammation in diabetes.

• 한국축산식품학회지
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• 제43권2호
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• pp.346-358
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• 2023

The aim of this study was to evaluate efficacies of selected lactic acid bacteria (LAB) in inducing immunoglobulin A (IgA) secretion. Twenty-five different LAB isolated from traditional fermented Korean foods were characterized for their probiotic properties and screened to identify those that could stimulate lamina propria cells (LPCs) from Peyer's patch to secret IgA in vitro. Among them, four strains (Lactiplantibacillus plantarum CJW55-10, Lactiplantibacillus pentosus CJW18-6, L. pentosus CJW56-11, and Pediococcus acidilactici CJN2696) were found to be strong IgA inducers. The number of IgA positive B cells and soluble IgA level were increased when LPCs were co-cultured with these LAB. Expression levels of toll-like receptor (TLR) such as TLR2 and TLR4 and secretion of interleuckin-6 were augmented in LPCs treated with these LAB. Further, we determined whether oral intake of these LAB enhanced IgA production in vivo. After one-week of daily oral administration, these LAB feed mice increased mucosal IgA and serum IgA. In conclusion, selected strains of LAB could induce systemic IgA secretion by activating lamina propria B cells in Peyer's patch and oral intake of selected strains of LAB can enhance systemic immunity by inducing mucosal IgA secretion.

• 생명과학회지
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• 제31권4호
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• pp.389-399
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• 2021

이 연구는 인간진피섬유아(HDF)세포에서 병풀 및 아시아티코사이드가 H₂O₂ 유래 세포주기 정지기, 미토콘드리아 활성 및 염증성 사이토카인에 미치는 영향을 조사하였다. 병풀 80% 메탄올 추출물, 에틸아세티이트 분획물 및 병풀의 대표물질인 아시아티코사이드를 사용하였다. 병풀 추추물, 에틸아세테이트 분획 및 아시아티코사이드로 처리한 세포는 낮은 수준의 TNF-α 및 IL-6을 분비하였고, 아시아티코사이드의 항산화 효과는 병풀 추출물 및 에틸아세테이트 분획물보다 높았다. 아시아티코사이드 처리는 미토콘드리아의 막포텐셜을 증가시키고, 미토콘드리아를 정상으로 되돌렸다. 스트레스 유도 후 에틸아세테이트 분획물 및 아시아티코사이드에 의해 미토콘드리아 산소 소비율이 증가하였고, TLR4-MyD88-TRAF6-p65 경로가 재감소하였다. 이러한 결과는 병풀 추출물, 에틸 아세테이트 분획 및 아시아티코사이드가 HDF 세포의 미토콘드리아 활성을 조절할 뿐 아니라 항산화 및 항염증에 효과 있음을 시사한다.