• Parasites, Hosts and Diseases
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• 제60권5호
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• pp.309-315
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• 2022

Inflammatory bowel disease (IBD) is a chronic and recurrent illness of the gastrointestinal tract. Treatment of IBD traditionally involves the use of aminosalicylic acid and steroids, while these drugs has been associated with untoward effects and refractoriness. The absence of effective treatment regimen against IBD has led to the exploration of new targets. Parasites are promising as an alternative therapy for IBD. Recent studies have highlighted the use of parasite-derived substances, such as excretory secretory products, extracellular vesicles (EVs), and exosomes, for the treatment of IBD. In this report, we examined whether EVs secreted by Giardia lamblia could prevent colitis in a mouse model. G. lamblia EVs (GlEVs) were prepared from in vitro cultures of Giardia trophozoites. Clinical signs, microscopic colon tissue inflammation, and cytokine expression levels were detected to assess the effect of GlEV treatment on dextran sulfate sodium (DSS)-induced experimental murine colitis. The administration of GlEVs prior to DSS challenge reduced the expression levels of pro-inflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. Our results indicate that GlEV can exert preventive effects and possess therapeutic properties against DSS-induced colitis.

• Journal of Acupuncture Research
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• 제39권1호
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• pp.40-48
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• 2022

Background: This study was performed to determine the effects of liposome-encapsulated bee venom (BV) treatment of inflammatory factors in atopic dermatitis (AD) compared with BV treatment. Methods: AD was induced by phthalic anhydride in mice and the effects of BV liposomes were measured. Using Leica Application Suite, thickened epidermis and dermis were measured after BV liposome treatment (0.05 and 0.1 ㎍/mL). The number of stained mast cells and the concentration of immunoglobulin (Ig)E were measured. Serum IgE concentration was analyzed using an enzyme-linked immunosorbent assay. The serum concentrations of interleukin (IL)-1, IL-4, and IL-6 inflammatory cytokines were measured. The levels of messenger ribonucleic acid expression of proinflammatory cytokines and chemokines were measured using reverse transcription polymerase chain reaction. Inhibition of mitogen-activated protein kinase activation, was analyzed on western blot. To measure the transcriptional activity (NF-κB inhibition by BV liposomes), western blots (p65, p-IκB, p50, and IκB) were also performed. Results: The weight of lymph nodes, serum IgE concentrations, morphological changes in the skins from the backs of the mice, and mast cell numbers in inflamed tissues were noticeably lower in the BV liposome treatment group compared with the BV treatment group. The concentrations of pro-inflammatory cytokines (IL-1, IL-4, IL-6) and chemokines (TSLP, CCL22) were also reduced. Activation of mitogen-activated protein kinase (p-ERK and p-p38), and transcriptional activity (p65, p-IκB, p50, and IκB) was strongly suppressed in the BV liposome group. Conclusion: BV liposomes may have a better therapeutic effect than BV for the treatment of AD.

• International Journal of Oral Biology
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• 제34권2호
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• pp.87-95
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• 2009

Porphyromonas gingivalis is a major etiologic agent of chronic periodontitis and cytokines produced by macrophages play important roles in the pathogenesis of periodontal diseases. In this study we investigated the cytokine response of phorbol myristate acetatedifferentiated THP-1 cells exposed to P. gingivalis. Compared with the prominent cell wall components of P. gingivalis (lipopolysaccharide and the major fimbrial protein FimA), live P. gingivalis stimulated much higher levels of cytokine production. In addition, whereas low multiplicity of infection challenges (MOI=10) of P. gingivalis 381 stimulated high levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and IL-1${\beta}$, high dose challenges with this bacterium (MOI = 100) resulted in a substantially diminished production of MCP-1 and IL-6. Moreover, high MOI P. gingivalis challenges achieved only low levels of induction of MCP-1 and IL-6 mRNA. The decreased production of MCP-1 and IL-6 appeared to be mediated by P. gingivalis proteases, because high MOI challenges with congenic protease mutant strains of this microorganism (MT10 and MT10W) did not result in a diminished production of MCP-1 and IL-6. Similar to its protease mutant strains, leupeptin (a protease inhibitor)- treated P. gingivalis at high doses induced high levels of MCP-1 production. To examine the mechanisms underlying the diminished production of MCP-1 by P. gingivalis proteases, the activation of mitogen-activated protein (MAP) kinases and NF-${\kappa}$B was compared between the 381 and MT10W strains. Whilst high doses of both 381 and MT10W similarly activated the three members of the MAP kinase family, the DNA binding activity of NF-${\kappa}$B, as revealed by gel shift assays, was greatly increased only by MT10W. Taken together, our data indicate that P. gingivalis stimulates the production of high levels of TNF-${\alpha}$, IL-1${\beta}$, IL-6, and MCP-1 but that high dose challenges with this bacterium result in a diminished production of MCP-1 and IL-6 via the protease-mediated suppression of NF-${\kappa}$B activation in THP-1 macrophagic cells.

• 대한화장품학회지
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• 제48권4호
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• pp.373-383
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• 2022

활성산소로 인한 염증 유발과 그로 인한 장벽손상은 꾸준히 주름생성의 원인으로 지목되어 왔다. 본 연구에서는 오갈피나무속에 속해있는 지리산오갈피와 가시오갈피, 오갈피나무, 오가나무 4종의 추출물에 대한 항산화, 항염증 및 피부 장벽개선, 항노화 관련 기능성 화장품 소재로서의 활용가치를 검증하고자 유효 지표성분 탐색과 효능 분석을 수행하였다. 먼저, 오갈피나무속 식물인 지리산오갈피와 가시오갈피, 오갈피나무, 오가나무 각각을 50% 에탄올을 용매로 추출, 농축, 동결건조 하여 시료를 제조하였다. 유효 지표성분탐색을 위해 주요 지표 성분인 eleutheroside E와 오갈피나무속에서 주로 검출되는 폴리페놀류 중 chlorogenic acid, caffeic acid 에 대하여 고성능 액체크로마토그래피를 통해 성분 함량을 측정하였으며, 오갈피나무속 중 지리산오갈피에서 eleutheroside E와 chlorogenic acid의 함량이 가장 높은 것을 확인하였다. 항산화활성은 DPPH 라디칼 소거활성이 지리산오갈피에서 가장 높았으며, 항염증 효능의 경우 LPS로 염증이 유발된 대식세포 내 NO 생성 억제 효능은 가시오갈피, 오가나무, 오갈피나무 추출물 100 ㎍/mL에서 각각 25%, 26%, 32% 일 때 지리산오갈피 추출물 100 ㎍/mL는 40% 억제 효능을 보였고 pro-inflammatory cytokine으로 알려진 IL-6 발현 억제 효능은 가시오갈피, 오가나무, 오갈피나무 추출물 100 ㎍/mL 농도에서 각각 20%, 36%, 23% 일 때 지리산오갈피 추출물 100 ㎍/mL는 41% 억제 효능을 보였다. 또한, 지리산오갈피 추출물 100 ㎍/mL에서 피부장벽 관련 인자인 filaggrin, involucrin의 발현이 각각 2.5 배, 1.6 배 증가되었으며, 주름관련 인자인 콜라겐분해효소는 29% 억제 효능을 나타내어 오갈피나무속 4 종 중 지리산오갈피는 피부의 염증 억제와 장벽강화, 주름개선용 화장품소재로써 활용가능하리라 판단된다.

• 생명과학회지
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• 제24권4호
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• pp.370-376
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• 2014

본 연구에서는 벼메뚜기 에탄올 추출물의 항염증 효능을 분석하기 위해 LPS로 염증 유도된 RAW 264.7 세포를 이용하였다. OCE의 항염증 효능을 확인 하기 위해서, 염증 유도된 RAW 264.7 세포에 대해 OCE 농도 의존적으로 염증성 사이토카인인 TNF-${\alpha}$와 IL-6의 유전자발현 및 단백질 생성을 감소시킴을 real-time PCR과 ELISA로 확인하였다. 또한, NF-${\kappa}B$ p65의 핵으로 이동이 차단됨을 면역형광염색으로 확인하였으며, iNOS와 COX-2 단백질 발현을 감소시키는 것을 Western blot 분석으로 확인하였다. 이상의 연구결과를 통해 벼메뚜기는 염증에 의한 NF-${\kappa}B$ p65의 활성과 TNF-${\alpha}$와 IL-6의 생성과 iNOS 및 COX-2의 발현을 억제하는 항염증 효능을 갖고 있는 것을 확인하였다.

• 대한한의학방제학회지
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• 제27권2호
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• pp.101-120
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• 2019

PURPOSE : Euonymi Lignum Suberalatum (EL) is the stem fin of Euonymi alatus. In traditional Korean medicine, EL is used for treatment of uterine bleeding, metritis and static blood. Recently, many studies have reported several pharmacological effects of EL including anticancer, antimicrobial, antidiabetic activity, and anti-oxidative stress. However, the mechanisms underlying anti-inflammatory effects by the EL is not established. METHODS : To investigate anti-inflammatory effects of Euonymi Lignum Suberalatum Water (ELWE), Raw 264.7 cells were pre-treated with $10-300{\mu}g/mL$ of ELWE, and then exposed to $1{\mu}g/mL$ of LPS. Levels of NO, IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were detected by ELISA kit. Expression of pro-inflammatory proteins were determined by immunoblot analysis. To evaluate the anti-inflammatory effect in vivo, rat paw edema volume, and expressions of COX-2 and iNOS proteins in carrageenan (CA)-induced rat paw edema model. RESULTS : NO production activated by LPS, was decreased by $30-300{\mu}g/mL$ of ELWE. Production of inflammatory mediators such as $TNF-{\alpha}$, ILs, $PGE_2$ were decreased by ELWE 100 and $300{\mu}g/mL$. In addition, ELWE reduced LPS-mediated iNOS and COX-2 expression. Moreover, ELWE increased $I-{\kappa}B{\alpha}$ expression in cytoplasm and decreased $NF-{\kappa}B$ expression in nucleus. In vivo study, ELWE reduced the increases of paw swelling, and expression of iNOS and COX-2 proteins in paw edema induced by CA injection. CONCLUSION : The results indicate that ELWE could inhibit the acute inflammatory response, via modulation of $NF-{\kappa}B$ activation. Furthermore, inhibition of rat paw edema induced by CA is considered as clear evidence that ELWE may be a useful source to treat acute inflammation.

• 한국자원식물학회지
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• 제34권1호
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• pp.31-36
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• 2021

본 연구는 망개나무 추출물의 항염증 효과를 구명하기 위하여 수행되었다. 망개나무를 이용한 다양한 기능성 연구가 진행되고 있으나 망개나무 항염증에 대한 연구는 과학적 근거가 부족한 실정이다. 따라서 망개나무 잎(BBK-L) 추출물이 마우스 대식세포인 RAW264.7 세포에서 LPS에 의한 염증반응에 미치는 영향을 평가하였다. LPS로 유도된 마우스 대식세포 RAW264.7에 BBK-L 추출물을 농도별로 처리하였을 때, NO 생성량과 만성염증 유발인자인 iNOS, COX-2, IL-1β, TNF-α및 IL-6 발현 감소를 확인하였으며, NF-κB 및 MAPK의 인산화를 억제하는 것을 확인하였다. 이러한 연구결과를 토대로 BBK-L 추출물이 만성 염증질환의 예방과 치료 또는 기능성 소재로 활용될 수 있는 기초적인 정보를 제공할 수 있을 것으로 사료된다.

• IMMUNE NETWORK
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• 제1권2호
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• pp.116-125
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• 2001

Background: Nitric oxide (NO) production has been described as a double-edged sword eliciting both pro- and anti-inflammatory effects in different immune reactions. This work was undertaken to investigate the immunoregulatory role of NO in experimental allergic encephalomyelitis (EAE) and experimental allergic uveitis (EAU). Method: We examined whether molsidomine (MSDM), a NO donor, administration to the myelin basic protein (MBP)- or interphotoreceptor retinoid binding protein (IRBP)-immunized rats could suppress EAE development by shifting toward the Th2 cytokine response. In the EAE experiments, the rats were treated orally with MSDM (10 mg/kg/day) at the early stage (-1~4 days) or throughout the experimental period (-1~15 days). Results: This resulted in significant amelioration of the disease and mild clinical symptoms, while MBP-immunization without MSDM administration showed severe EAE development. A marked reduction in inflammation was also observed in the spinal cord, indicating the crucial role of NO in the pathogenesis of EAE in in vivo. In the EAU experiments, a 24 h pre-treatment with MSDM prior to IRBP immunization resulted in significant inhibition of the disease. Furthermore, MSDM administration for 2 1 days completely reduced the incidence and severity of EAU. To investigate whether MSDM could modulate cytokine switching from Th 1 to Th2, culture supernatants of MBP- or IRBP-stimulated inguinal lymphocytes were analyzed. MSDM treatment enhanced IL-10 secretion but decreased IFN-${\gamma}$. IL-4 was undetectable in all groups. In contrast, the MBP-or IRBP-immunized rats without MSDM secreted high concentrations of IFN-${\gamma}$, but low concentrations of IL-10. Conclusion: In conclusion, NO administation suppresses EAE and EAU by modulating the Th1/Th2 balance during inflammatory immune responses. This work further suggests that NO may be useful in the therapeutic control of autoimmune disease.

• 생명과학회지
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• 제16권3호
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• pp.500-504
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• 2006

합토글로빈(Hp)은 조직손상이나 감염 등의 염증시에 혈중 농도가 증가하는 급성기반응단백질로서 주로 간에서 생합성되지만 염증을 동반한 폐에서도 발현됨이 보고되었다. 폐에서 합성되는 Hp이 염증반응에 어떤 영향을 주는지를 조사하고자, Hp을 과발현하는 폐상피세포를 사용하여 COX-2 및 염증관련 cytokine들의 발현을 조사하였다. Stable transfection 또는 transient transfection된 A549 세포에서 Hp이 잘 발현되고 있음을 확인한 후 COX-2의 발현을 측정한 결과, Hp의 과발현에 의해 COX-2 합성이 현저히 증가함을 확인할 수 있었다. 또한 Hp을 과발현하는 A549세포에 LPS ($1{\mu}g/ml$) 또는 $IL-1{\beta}$ (100 U/ml)를 각각 24시간 동안 처치하였을 때, Hp에 의한 COX-2 발현 증가는 LPS또는 $IL-1{\beta}$자극에 의해 협동적으로 증가하였다. ACP-based PCR 방법으로 염증관련 cytokine들의 발현을 측정한 결과, Hp에 의해 SPARC의 발현이 현저히 저하되는 반면에 IL-4 및 S100A1 유전자 발현은 약간 증가함을 알 수 있었다. 이러한 결과들은 폐상피세포에서 Hp이 염증반응을 활성화시키는 기전으로 작용함을 시사한다.

• 생명과학회지
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• 제33권4호
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• pp.349-356
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• 2023

만성 염증성 관절염 질환인 통풍은 고요산혈증을 특징으로 하며 NLRP3 inflammasome의 활성화에 따른 IL-1β와 같은 염증성 cytokine 방출과 연관된 MSU에 대한 염증 반응에 의해 유발될 수 있다. 마늘에 함유된 황 함유 화합물은 다양한 질병에 대한 잠재적인 유익한 약리학적 효능을 가지지만, NLRP3 inflammasome 활성화와 연관된 통풍 억제에 대한 효능은 현재까지 입증되지 않았다. 본 연구에서는 대표적인 마늘 유래 황화합물인 DADS와 DATS가 MSU에 의한 NLRP3 inflammasome 활성을 억제할 수 있는지를 조사하였다. 본 연구의 결과에 의하면, 비세포 독성 조건에서 DADS와 DATS는 LPS가 전처리된 RAW 264.7 대식세포에서 MSU에 대한 반응으로 증가된 NO의 생성과 IL-1β 유리를 유의적으로 차단하였다. DADS와 DATS는 또한 증가된 NLRP3, ASC, caspase-1 p20 및 IL-1β의 발현을 감소시켰으며, 이는 MSU로 유도된 LRP3 inflammasome 활성화가 DADS와 DATS에 의해 억제되었음을 의미한다. 아울러, DADS와 DATS는 NLRP3 inflammasome 활성화에 상위 신호로 작용하는 산화적 스트레스를 차단했으며 ROS 생성을 제거한다는 사실에서 입증되었다. 결론적으로, 본 연구의 결과는 DADS와 DATS가 ROS/NLRP3 경로를 억제하여 inflammasome 활성화를 차단함으로서 NLRP3 의존성 통풍성 관절염 치료를 위한 잠재력이 우수함을 의미한다.