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Roh, Kyung-Baeg,Kim, Chan-Hee,Lee, Hanna,Kwon, Hyun-Mi,Park, Ji-Won,Ryu, Ji-Hwan,Kurokawa, Kenji,Ha, Nam-Chul,Lee, Won-Jae,Lemaitre, Bruno,Sö,derhä,ll, Kenneth,Lee, Bok-Luel American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.29
<P>The insect Toll signaling pathway is activated upon recognition of Gram-positive bacteria and fungi, resulting in the expression of antimicrobial peptides via NF-kappaB-like transcription factor. This activation is mediated by a serine protease cascade leading to the processing of Spätzle, which generates the functional ligand of the Toll receptor. Recently, we identified three serine proteases mediating Toll pathway activation induced by lysine-type peptidoglycan of Gram-positive bacteria. However, the identities of the downstream serine protease components of Gram-negative-binding protein 3 (GNBP3), a receptor for a major cell wall component beta-1,3-glucan of fungi, and their order of activation have not been characterized yet. Here, we identified three serine proteases that are required for Toll activation by beta-1,3-glucan in the larvae of a large beetle, Tenebrio molitor. The first one is a modular serine protease functioning immediately downstream of GNBP3 that proteolytically activates the second one, a Spätzle-processing enzyme-activating enzyme that in turn activates the third serine protease, a Spätzle-processing enzyme. The active form of Spätzle-processing enzyme then cleaves Spätzle into the processed Spätzle as Toll ligand. In addition, we show that injection of beta-1,3-glucan into Tenebrio larvae induces production of two antimicrobial peptides, Tenecin 1 and Tenecin 2, which are also inducible by injection of the active form of Spätzle-processing enzyme-activating enzyme or processed Spätzle. These results demonstrate a three-step proteolytic cascade essential for the Toll pathway activation by fungal beta-1,3-glucan in Tenebrio larvae, which is shared with lysine-type peptidoglycan-induced Toll pathway activation.</P>
노경백 ( Kyung-baeg Roh ),신승우 ( Seoungwoo Shin ),윤소현 ( Sohyun Yoon ),원진배 ( Jin Bae Weon ),오세영 ( Se-young Oh ),김준오 ( Junoh Kim ),박덕훈 ( Deokhoon Park ),정은선 ( Eunsun Jung ) 대한화장품학회 2020 대한화장품학회지 Vol.46 No.4
아토피성 피부염은 피부장벽 기능장애, 염증 및 만성 소양증을 특징으로 하는 다인성의 염증성 피부질환이다. 아토피성 피부염은 유전적, 면역학적, 환경적 요인 등의 복합적인 요인으로 피부장벽 기능과 면역기능의 장애를 유발한다고 알려져 있다. 고삼 추출물은 중국전통의학에서 사용되고 있으나, 이의 항아토피 효능에 대한 연구는 거의 진행되지 않았다. 본 연구에서는 아토피성 피부염의 주요 증상인 피부장벽 기능과 면역이상 개선에 대한 고삼추출물의 효과를 평가하였다. 고삼추출물은 피부장벽 기능에서 중요한 역할을 하는 각질세포막의 형성을 강화하는 결과를 나타내었다. 또한 피부의 보습작용에 있어서 중요한 히알루론산의 발현을 증가시키는 결과를 나타내었다. 아토피성 피부염 병변에서 특이적으로 증가하는 황색포도상구균에 대한 고삼추출물의 효능도 확인하였으며, 고삼추출물이 황색포도상구균으로부터 유도된 전염증성사이토카인의 생성을 억제함을 확인하였다. 또한 피부 스트레스 등으로 부터 생성되는 신경전달 물질인 substance P에 의해 유도된 전염증성사이토카인의 발현도 억제하는 것을 확인하였다. 이러한 결과들은 고삼추출물이 피부장벽기능과 면역반응 개선을 통해 아토피 피부염 치료에 사용될 수 있는 잠재적 후보물질임을 제시한다. Atopic dermatitis (AD) is a common and multifactorial inflammatory skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. AD has a complex etiology that includes genetic, immunological, and environmental factors that cause skin barrier abnormalities and immune dysfunctions. Sophora flavescens (SF) has been used in traditional Chinese medicine, but little research has been conducted on its anti-AD efficacy. In this study, we evaluated the effect of SF extract (SFE) on improving skin barrier function and immune abnormalities, which are the main symptoms of AD. SFE has the capacity to enhance the formation of cornified envelope (CE) that plays an important role in the skin barrier function. In addition, it was confirmed that SFE increased the expression of hyaluronic acid related to skin moisture. The effect of SFE against Staphylococcus aureus (S. aureus), which increases specifically in AD lesions, confirmed that SFE inhibited the production of pro-inflammatory cytokines induced by S. aureus. Furthermore, SFE was shown to inhibit the expression of pro-inflammatory cytokines induced by substance P (SP), the cause of skin neurogenic inflammation. These results demonstrate that SFE could be one of potential candidate agent for the treatment of AD by improving the skin barrier function and immune responses.
노경백 ( Kyung-baeg Roh ),이정아 ( Jung-a Lee ),박준호 ( Junho Park ),정광선 ( Kwangseon Jung ),정은선 ( Eunsun Jung ),박덕훈 ( Deokhoon Park ) 대한화장품학회 2017 대한화장품학회지 Vol.43 No.2
떡쑥(Gnaphalium affine D. Don, GA)은 동아시아 지역에서 식용으로 사용되고 있으며, 예로부터 전통적인 민간요법 약재로 사용되어 왔다. 현재 떡쑥 추출물(GA extract, GAE)의 항산화 활성과 항보체 활성 등은 알려져 있으나, 항염과 항알러지 효능 및 그 작용 기작은 자세히 알려져 있지 않다. 본 연구에서는 염증 매개인자인 산화질소, 프로스타글란딘 E<sub>2</sub>, Toll-유사수용체 4, 에오탁신-1, 히스타민의 활성화에 대한 GAE의 저해효과를 평가하였다. 본 연구를 통해, GAE는 유도성 산화질소 합성효소와 COX-2의 발현을 저해함을 확인하였으며, 이를 통해 산화질소와 프로스타글란딘 E<sub>2</sub>의 생성을 저해함을 확인하였다. GAE는 LPS로부터 유도된 Toll-유사수용체 4의 발현에도 영향을 미치는 것을 확인하였으며, A23187로부터 유도되는 비만세포의 히스타민 방출의 억제에도 효과적으로 작용하는 것을 확인하였다. 또한 IL-4로부터 유도된 에오탁신-1의 생성도 효과적으로 억제하는 결과를 확인하였다. 이상의 결과로부터 GAE는 항염증과 항알러지 효능을 가진다고 사료되며, 향후 항염증 및 항알러지 화장품 원료로서의 이용가능성을 보였다. Gnaphalium affine D. DON (GA) has been used as a vegetable as well as a folk medicine in East Asia. The antioxidant and anti-complementary activity of GA extract (GAE) has also been reported. However, little is known about its anti-inflammatory and anti-allergic effect and mechanism of action. In this study, we evaluated the inhibitory effects of GAE on the production of inflammatory mediators such as NO, PGE<sub>2</sub>, TLR4, eotaxin-1 and histamine. Our results suggest that GAE inhibits the production of NO and PGE<sub>2</sub> by inhibiting transcriptional activation via the involvement of iNOS and COX-2. The LPS-induced expression of Toll-like receptor 4 (TLR4) was also attenuated. In addition, GAE inhibited A23187-induced histamine release from MC/9 mast cells. It also inhibited the production of eotaxin-1 induced by IL-4. Collectively, these results suggest that GAE may have considerable potential as a cosmetic ingredient with anti-inflammatory and anti-allergic properties.
노경백 ( Kyung-baeg Roh ),신영희 ( Ying-ji Xin ),박덕훈 ( Deokhoon Park ),정은선 ( Eunsun Jung ) 대한미용학회 2021 대한미용학회지 Vol.17 No.4
In the treatment of chronic inflammatory skin diseases, topical steroids are known to show strong efficacy in relieving inflammation. Nevertheless, because its use in treatment is limited due to the side effects of long-term use, development of a therapeutic agent using natural products is necessary. Studies on various natural products with antiinflammatory effects are currently being conducted, however few studies verifying the anti-inflammatory effect of natural products through direct comparison with steroids have been reported. In this study, the anti-inflammatory effect of BSASM, a complex of seven natural products, and hydrocortisone, a topical steroid, were directly compared, and the effectiveness of BSASM as an anti-inflammatory agent was evaluated. Compared with hydrocortisone (topical steroids), BSASM had a similar inhibitory effect on the production of nitric oxide and prostaglandin E2, and showed a better inhibitory effect than hydrocortisone in inhibiting the production of pro-inflammatory cytokines, TNF-α and IL-6. In addition, mRNA expression of collagen type I alpha 1 was decreased by hydrocortisone in human dermal fibroblasts, which is associated with skin atrophy, however expression of COL1A1 was not affected by BSASM. Based on these results, it is expected that BSASM can be applied as a natural alternative to hydrocortisone in treatment of chronic inflammatory skin diseases.
Anti‑acne effects of Castanea crenata bur extract and identification of active compound
You Jiyoung,Ji Hyanggi,Roh Kyung-Baeg,Cho Eunae,Chajra Hanane,Frechet Mathilde,Park Deokhoon,Jung Eunsun 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.1
Acne vulgaris is a common disease of the pilosebaceous unit. Hyperseborrhea, a follicular colonization by Cutibacterium acnes and a complex inflammatory state are pathogenic factors of acne vulgaris. In the present study we investigated the anti-acne efficacy of Castanea crenata bur extract (CBE) in vitro and searched active compound for mitigating hyperseborrhea. In sebocytes, CBE inhibited the sebum synthesis through downregulation of sterol response element-binding protein-1 and peroxisome proliferator-activated receptor γ expression. CBE also inhibited the 5-alpha reductase activity which is associated with androgen-induced sebum production. Moreover, CBE showed anti-inflammatory effect in C. acnes and free fatty acid-induced inflammatory condition through suppressing Toll-like receptor 2 activity. Anti-inflammatory effect was also observed in keratinocytes via inhibition of NF-κB translocation into nuclei. Finally, we identified the ellagic acid as an active compound for inhibiting sebum production in CBE. These findings suggest that CBE have potential to be a multi-target agent for acne vulgaris and a good source of ellagic acid as an anti-sebum compound.
Kurokawa, Kenji,Lee, Hanna,Roh, Kyung-Baeg,Asanuma, Miwako,Kim, Young Sook,Nakayama, Hiroshi,Shiratsuchi, Akiko,Choi, Youngnim,Takeuchi, Osamu,Kang, Hee Jung,Dohmae, Naoshi,Nakanishi, Yoshinobu,Akira, American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.13
<P>Some synthetic lipopeptides, in addition to native lipoproteins derived from both Gram-negative bacteria and mycoplasmas, are known to activate TLR2 (Toll-like receptor 2). However, the native lipoproteins inherent to Gram-positive bacteria, which function as TLR2 ligands, have not been characterized. Here, we have purified a native lipoprotein to homogeneity from Staphylococcus aureus to study as a native TLR2 ligand. The purified 33-kDa lipoprotein was capable of stimulating TLR2 and was identified as a triacylated SitC lipoprotein, which belongs to a family of ATP binding cluster (ABC) transporter substrate-binding proteins. Analyses of the SitC-mediated production of cytokine using mouse peritoneal macrophages revealed that the SitC protein (3 nm) induced the production of tumor necrosis factor-alpha and interleukin-6. Moreover, analysis of knock-out mice showed that SitC required TLR2 and MyD88, but not TLR1 or TLR6, for the induction of cytokines. In addition to the S. aureus SitC lipoprotein, we purified two other native ABC transporter substrate-binding lipoproteins from Bacillus subtilis and Micrococcus luteus, which were both shown to stimulate TLR2. These results demonstrate that S. aureus SitC lipoprotein is triacylated and that the ABC transporter substrate-binding lipoproteins of Gram-positive bacteria function as native ligands for TLR2.</P>