Association of DOCK8, IL17RA, and KLK12 Polymorphisms with Atopic Dermatitis in Koreans

( Won Il Heo ),( Kui Young Park ),( Mi-kyung Lee ),( Yu Jeong Bae ),( Nam Ju Moon ),( Seong Jun Seo ) 대한피부과학회 2020 Annals of Dermatology Vol.32 No.3

Background: Early-onset and severe atopic dermatitis (AD) in patients increase the probability of the development of allergic rhinitis or asthma. Treatment and prevention strategies in infants and young children with AD are targeted toward treating the symptoms, restoring skin barrier functions, and reducing the absorption of environmental allergens in an attempt to attenuate or block the onset of asthma and food allergy. Objective: Given that the initiating events in AD remain poorly understood, identifying those at risk and implementing strategies to prevent AD is necessary. Methods: Whole-exome sequencing (WES) was performed in a 43 control group and a disease group with 20 AD patients without atopic march (AM) and 20 with AM. Sanger sequencing was carried out to validate found variants in cohorts. Results: DOCK8, IL17RA, and KLK12 single-nucleotide polymorphisms were identified by WES as missense mutations: c.1289C>A, p.P97T (rs529208); c.1685C>A, p.P562G (rs12484684); and c.457+27>C, rs3745540, respectively. A case-control study show that total immunoglobulin E (IgE) level was significantly increased in the AA genotype of DOCK8 compared to the CA genotype in allergic patients. The rs12484684 of IL17RA increased risk of adult-onset AD (odds ratio: 1.63) compared to the control for (A) allele frequency. AD and AM Patients with the IL17RA CA genotype also had elevated IgE levels. rs3745540 of KLK12 was associated with AD in dominant model (odds ratio: 2.86). Conclusion: DOCK8 (rs529208), IL17RA (rs12484684), and KLK12 (rs3745540), were identified using a new WES filtering method. the result suggests that polymorphism of DOCK8 and IL17RA might be related to increase the total IgE level. (Ann Dermatol 32(3) 197∼205, 2020)

Effects of the water of yellow soil, Ji-Jang-Soo on cell viability and cytokines production in immune cells

Jeong, Hyun-Ja,Hwang, Gab-Soo,Myung, No-Il,Lee, Joon-Ho,Lee, Ju-Young,Um, Jae-Young,Kim, Hyung-Min,Hong, Seung-Heon Kyung Hee Oriental Medicine Research Center 2006 Oriental pharmacy and experimental medicine Vol.6 No.1

Ji-Jang-Soo (JJS) is known to have a detoxification effect. However, it is still unclear how JJS has these effects in experimental models. In this study, we investigated the effect of JJS on the viability of cells and production of cytokines in human T-cell line, MOLT-4 cells, and human mast cell line, HMC-1 cells. The MOLT-4 cells were cultured for 24 h in the presence or absence of JJS. As the result, JJS (1/100 dilution) significantly increased the cell viability about 78% (P < 0.05) and also increased the interleukin (IL)-2, and interferon $(IFN)-{\gamma}$ production compared with media control at 24 h. But had no effect on IL-4 production. Hypoxia mimic compound, desferroxamine (DFX) decreased the immune cell viability. Cell viability decreased by DFX was increased by JJS. In conclusion, these data indicate that JJS may have an immune-enhancing effect.

RAW 264.7 cell에서 생강나무 가지 추출물의 항염증 효과

이주형 ( Ju Hyung Lee ),이진아 ( Jin A Lee ),김민주 ( Min Ju Kim ),정일하 ( Il-ha Jeong ),노성수 ( Seong-soo Roh ) 한약응용학회 2022 한약응용학회지 Vol.22 No.1

Objective : This study aimed to investigate the activity according to the extraction method of Lindera obtusilba Bulme Twig (LO) in lipopolysaccharide (LPS) -induced RAW264.7 cells. Method : The methods of the two extractions included 70% ethanol and boiling in water (water extract, LOW; 70% ethanol extract, LOE). Total polyphenol, total flavonoid, EPPH and ABTS radical scavenging assays were performed to compare in vitro antioxidant effects. LOW and LOE (50, 100, and 200μg/mL) were applied to 0.1 μ g/mL LPS-induced RAW 264.7 macrophages in vitro. The level of nitric oxide (NO) and pro-inflammatory cytokines in the supernatant fraction were determined using Gress regent and the enzyme-linked immunosorbent assay (ELISA). The mitogen-activated protein kinase (МАРК) subgroups extracellular signal-regulated kinase (ERK), С-Jun N-terminal kinase (JNK), and p38 activation in extracts were detected via Western blot. Moreover, mRNA levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were measured using Real-time polymerase chain reaction (qPCR). Result : The increased NO level in the bPS-only-treated group was inhibited in a concentration―dependent manner by the treatment of two samples. Among the inflammatory cytokines, TNF-α was significantly inhibited only in the LOE (100 and 200 g/mL), but IL-1β and IL-6 were significantly inhibited in a concentration―dependent manner in all drug treatment groups. The protein expressions of MAPKs (ERK, JNK, and p―38) showed that the LOW treatment affected only p-ERK whereas the ELT treatment affected all three factors. In particular, it was confirmed that the levels of COX-2 and iNOS mRNA were more dominant in the LOE treatment than in the LOW treatment. Conclusions : Our findings indicate that the LOE treatment exerted a superior anti-inflammatory effect on inflammation induced by LPS than the LOW treatment in the occurrence of inflammation.

들깨(Perilla frutescens) 새싹 추출물의 항산화 및 항염 효과

정승일(Seung-Il Jeong),김현수(Hyeon Soo Kim),전인화(In Hwa Jeon),강현주(Hyun Ju Kang),목지예(Ji Ye Mok),천춘진(Chun Jin Cheon),유현희(Hyeon Hee Yu),정선일(Seon Il Jang) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.1

본 연구는 들깨 새싹 추출물의 항산화, 항염증 및 항부종에 대한 효과를 조사하였다. 들깨 새싹 추출물은 DPPH와 ABTS 라디칼을 효과적으로 제거하는 항산화 활성이 우수하였다. 또한 들깨 새싹 추출물은 활성화된 설치류 유래 대식세포주인 RAW 264.7세포와 인간 유래 HMC-1 세포의 TNF-α와 IL-1β를 효과적으로 억제하였다. 더욱이 마우스의 귀와 발 부종을 억제하는 우수한 효과가 있었다. 이러한 결과는 들깨 새싹 추출물은 항산화제로 사용될 수 있을 뿐만 아니라 항염증과 항부종에 효과적인 물질이라는 것을 제시해주었다. 이와 관련된 들깨 새싹 추출물의 기능성에 대해서는 앞으로 분자생화학적 수준에서 더 연구해야할 필요성이 있는 것으로 사료된다. We investigated the effects of an ethanol extract from Perilla frutescens sprouts (PFSE) as an antioxidant, and its effects on edema and inflammation in RAW 264.7 cells and HMC-1 cells. The antioxidant activities (DPPH and ABTS radical scavenging) of PFSE were similar to those of butylated hydroxytoluene (BHT) and (±)-6-hydroxy-2,5,7,8- tetramethylchromane-2-carboxylic acid (Trolox). We also investigated the anti-inflammatory effects of PFSE on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and HMC-1 cells stimulated with phorbol 12-myristate 13-acetate (PMA) with the calcium ionophore A23187. TNF-α and IL-1β production, which had been increased by treatment with LPS or PMA plus A23187, were significantly inhibited by PFSE in a dose-dependent manner. Furthermore, PFSE significantly reduced the xylene-induced ear edema and the carrageenan-induced paw edema of ICR mice in a dosedependent manner. The effects of PFSE (200 mg/kg) in reducing ear and paw edema were similar to those of aspirin (50mg/kg). These results suggest that PFSE can be potentially used as a medicine for treating oxidative stress, an edematous and inflammatory disease.

Naringin Protects Ovalbumin-induced Asthma through the Down-regulation of MMP-9 Activity and GATA-3 Gene

Chang-Min Lee(이창민),Jeong Hyun Chang(장정현),In Duk Jung(정인덕),Young-Il Jeong(정영일),Noh Kyung Tae(노경태),Hee-ju Park(박희주),Jong-Suk Kim(김종석),Yong Kyoo Shin(신용규),Sung Nam Park(박성남),Yeong-Min Park(박영민) 한국생명과학회 2009 생명과학회지 Vol.19 No.6

Naringin은 레몬, 오렌지에서 발견되는 flavonoid계열에 속하는 물질로 여러 식물과 과일에 다량 함유되어 있다. 항암, 항산화 작용을 하는 것으로 알려져 있는 Naringin을 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델을 이용하여 치료효과를 알아 보았다. 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포(Th2 cell)가 생산하는 IL-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 또한, 최근에 Th1/Th2 전사인자로서 GATA-3가 밝혀졌는데 이번 실험에서 Naringin이 ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1, Th2 싸이토카인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토카인(IL-4, IL-5)의 증가가 관찰되었다. 그러나 Naringin을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 Naringin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 Naringin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다. The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.

The optimal duration of ischemic preconditioning for renal ischemia-reperfusion injury in mice

Hyun Su Choi,Jeong Kye Hwang,Jeong Goo Kim,Hyeon Seok Hwang,Sang Ju Lee,Yoon kyung Chang,Ji Il Kim,In Sung Moon 대한외과학회 2017 Annals of Surgical Treatment and Research Vol.93 No.4

Purpose: The aim of the present study was to investigate the protective effects of ischemic preconditioning for different periods of time and to elucidate the optimal safe ischemic preconditioning time for renal ischemia-reperfusion (I/R) injury in mice. Methods: A total of 25 male C57BL/6 mice were randomly divided into 5 groups (sham, I/R, ischemic preconditioning [IP]-3, IP-5, and IP-7 groups), in which the kidney was preconditioned with IP of various durations and then subjected to I/R injury (the last 3 groups). To induce renal ischemia, the left renal pedicle was occluded with a nontraumatic microaneurysm clamp for 30 minutes followed by reperfusion for 24 hours. The effects of IP on renal I/R injury were evaluated in terms of renal function, tubular necrosis, apoptotic cell death and inflammatory cytokines. Results: Results indicated that BUN and creatinine (Cr) levels increased significantly in the I/R group, but the elevations were significantly lower in IP groups, especially in the IP-5 group. Histological analysis revealed that kidney injury was markedly decreased in the IP-5 group compared with the I/R group, as evidenced by reduced renal necrosis/apoptosis. In addition, IP significantly inhibited gene expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokines (monocyte chemoattractant protein-1). Western blot analysis indicated that the expression levels of Toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-kB) were upregulated in the I/R group, while expression was inhibited in the IP groups. Conclusion: Five-minute IP had the greatest protective effect against I/R injury.

H₂O₂ 유도 U2OS 세포에서 Pinus sylvestris L.의 산화적 스트레스 및 골관절염 개선 효과

신미래(Mi-Rae Shin),최정원(Jeong Won Choi),김민주(Min Ju Kim),안희연(Hui Yeon An),유지헌(Ji Heon Yu),정일하(Il Ha Jeong),유왕근(Wang Keun Yoo),Bold Sharavyn,노성수(Seong-Soo Roh) 한국식품영양과학회 2024 한국식품영양과학회지 Vol.53 No.5

LPS로 유도한 대식세포의 염증반응에서 우슬의 항염증 효과

김민선 ( Min Sun Kim ),정진수 ( Jin Soo Jeong ),이혜윤 ( Hye Youn Lee ),주영승 ( Young Sung Ju ),배기상 ( Gi Sang Bae ),서상완 ( Sang Wan Seo ),조일주 ( Il Joo Cho ),박성주 ( Sung Joo Park ),송호준 ( Ho Joon Song ) 대한본초학회 2011 大韓本草學會誌 Vol.26 No.2

Objectives: Achyranthes japonica (AJ ) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that AJ could show the anti-inflammatory effects in macrophages. In this experiment, we studied whether AJ could inhibit the inflammatory responses in macrophages. Methods: To measure out the cytotoxicity of AJ, we performed the MTT assay. We evaluated the nitric oxide (NO) production, and cytokine production such as interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF)-a. We also investigated the cellular mechanims such as mitogen activated protein kinases (MAPK)s and nuclear factor kappa B (NF-kB). Results: AJ inhibited lipopolysaccharide (LPS)-induced NO production. AJ also inhibited production levels of IL-1b, IL-6 and TNF-a in LPS-stimulated macrophage. Finally, western blot analysis showed that AJ treatment inhibited the activation of p38 but not of extracellular signal-regulated kinase, c-jun NH2-terminal kinase and NF-kB. Conclusions: These results showed that AJ down-regulated the inflammatory response via p38 in macrophages, which suggest that AJ could be a candidate on treating inflammatory diseases.

류마티스 활막염에 있어 염증매개물질에 의한 Transforming Growth Factor-β-inducible Gene-h3 (βig-h3) 생산 조절 기전

강영모 ( Young Mo Kang ),김성일 ( Sung Il Kim ),김정섭 ( Jeong Seup Kim ),유동완 ( Dong Wan You ),사금희 ( Kheum Hee Sa ),박은주 ( Eun Ju Park ),김성욱 ( Sung Uk Kim ),서재석 ( Jae Seok Seo ),한승우 ( Seung Woo Han ),남언정 ( Eon 대한류마티스학회 2005 대한류마티스학회지 Vol.12 No.2

Objective: To investigate the expression pattern of transforming growth factor-β-inducible gene-h3 (βig-h3) within rheumatoid synovial tissue and the regulation of βig-h3 synthesis in fibroblast-like synoviocyte (FLS). Methods: Synovial tissues obtained from patients with rheumatoid arthritis and osteoarthritis were obtained during joint replacement surgery. βig-h3 expression was evaluated with immunohistochemical stain. FLS was isolated from synovial tissues and stimulated with cytokines including TGF-β, TNF-α, IL-1β, IFN-γ, IL-6, IL-4, and IL-10. βig-h3 synthesis was measured using semiquantitative RT-PCR, ELISA, immunofluorescence stain, and flow cytometry. Results: Expression of βig-h3 was diffuse and abundant in both lining and sublining layers of rheumatoid synovium, which was more prominent than those of osteoarthritis. Production of βig-h3 in FLS was regulated by TGF-β1 in a dose-dependent manner and was highest at 5 ng/mL of TGF-β1. TNF-α and IL-1β upregulated the production of βig-h3 from FLS synergistically with TGF-β1 but other cytokines such as IL-4, IL-6, IL-10 did not affect. βig-h3 synthesis was efficiently inhibited by dexamethasone at higher dose (100 nM) but not by cyclosporine-A. Conclusion: Production of βig-h3, which is highly upregulated in rheumatoid synovitis, is differentially regulated by inflammatory cytokines.

Suppression of lipopolysaccharide-induced expression of inflammatory indicators in RAW 264.7 macrophage cells by extract prepared from <i>Ginkgo biloba</i> cambial meristematic cells

Jang, Sun-Hee,Lee, Eun Kyung,Lim, Min Jung,Hong, Nam Ju,Oh, Il Seok,Jin, Young Woo,Jeong, Han-Sol,Jeong, Yong-Seob,Lee, Jeong-Chae,Jang, Yong-Suk Informa Healthcare 2012 PHARMACEUTICAL BIOLOGY Vol.50 No.4

<P><I>Context</I>: <I>Ginkgo biloba</I> L. (Ginkgoaceae) leaves have been used as an herbal medicine that has a complex range of biological activities. However, when we consider that biological activity of plant extracts is highly variable according to the source, location, and harvest season, technology to obtain the natural products with homogeneity is extremely important.</P><P><I>Objective</I>: We established the technology to obtain the cambial meristematic cells (CMCs) of <I>Ginkgo biloba</I>, which were expanded <I>in vitro</I> with homogeneity through a suspension culture and then determined the anti-inflammatory activity of fractionated samples prepared from the ethanol extract of CMCs.</P><P><I>Materials and methods</I>: We determined the anti-inflammatory activity of samples using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Especially, influence of sample treatment on the expression of various indicators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, mitogen-activated protein (MAP) kinases, transcription factor, and cytokines, involved in inflammatory activity was assessed.</P><P><I>Results</I>: A fractionated sample demonstrated 53.4% inhibition of LPS-induced NO production from the cells. Additionally, when fractionated samples were treated, iNOS and COX-2 expressions were almost completely suppressed. Fractionated samples also inhibited the phosphorylation of LPS-induced extracellular signal-regulated (ERK) and p38 MAP kinases more than 60%. IκB phosphorylation and subsequent nuclear factor (NF)-κB activation were also suppressed by fractionated samples. The expression of pro-inflammatory cytokines, IL-6 and tumor necrosis factor (TNF)-α, was significantly inhibited by the sample treatment.</P><P><I>Discussion and conclusion</I>: Fractionated samples from the ethanol extract of <I>Ginkgo biloba</I> CMCs could potentially be the source of a powerful anti-inflammatory substance.</P>