Glucocorticoid-induced tumor necrosis factor receptor–related protein co-stimulation facilitates tumor regression by inducing IL-9–producing helper T cells

Kim, Il-Kyu,Kim, Byung-Seok,Koh, Choong-Hyun,Seok, Jae-Won,Park, Jun-Seok,Shin, Kwang-Soo,Bae, Eun-Ah,Lee, Ga-Eun,Jeon, Hyewon,Cho, Jaebeom,Jung, Yujin,Han, Daehee,Kwon, Byoung S,Lee, Ho-Young,Chung, Nature Publishing Group, a division of Macmillan P 2015 Nature medicine Vol.21 No.9

<P>T cell stimulation via glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) elicits antitumor activity in various tumor models; however, the underlying mechanism of action remains unclear. Here we demonstrate a crucial role for interleukin (IL)-9 in antitumor immunity generated by the GITR agonistic antibody DTA-1. IL-4 receptor knockout (Il4ra(-/-)) mice, which have reduced expression of IL-9, were resistant to tumor growth inhibition by DTA-1. Notably, neutralization of IL-9 considerably impaired tumor rejection induced by DTA-1. In particular, DTA-1-induced IL-9 promoted tumor-specific cytotoxic T lymphocyte (CTL) responses by enhancing the function of dendritic cells in vivo. Furthermore, GITR signaling enhanced the differentiation of IL-9-producing CD4(+) T-helper (T(H)9) cells in a TNFR-associated factor 6 (TRAF6)- and NF-kappa B-dependent manner and inhibited the generation of induced regulatory T cells in vitro. Our findings demonstrate that GITR co-stimulation mediates antitumor immunity by promoting T(H)9 cell differentiation and enhancing CTL responses and thus provide a mechanism of action for GITR agonist-mediated cancer immunotherapies.</P>

감껍질 열수 및 초임계 유체 추출물의 항아토피 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),방숭주(Chong Zhou Fang),신재영(Jae Young Shin),하혜옥(Hye Ok Ha),김상준(Sang Jun Kim),정승일(Seung Il Jeong),장선일(Seon Il Jang) 한국식품과학회 2015 한국식품과학회지 Vol.47 No.3

본 연구에서는 고종시 감껍질을 열수 추출 및 초임계 유체 추출하여 아토피 피부염 증상 억제 효과를 밝히고, 항염 효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 홍반(erythema), 가려움과 피부의 건조상태(pruritus and dry skin), 부종과 혈종(edema and excoriation), 짓무름(erosion), 그리고 태선화(lichenification)와 같은 아토피 피부염 같은 증상이 AD 모델에서 증가하였지만, SPPE와 PPWE를 투여하였을 경우 완화되는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증 세포의 침윤은 AD 모델에서 크게 증가하였지만, SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 혈청 중의 IgE와 IL-4의 수치를 측정한 결과, AD 모델에서 크게 증가하였으나 SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어나게 억제하는 효과를 나타내었다. 또한 RAW264.7 세포에 SPPE를 처리하였을 경우 염증매개 인자인 NO, PGE2, IL-6, IL-1β의 생성량이 유의적의로 감소하였고, PPWE의 경우 NO, PGE2, IL-1β의 생성을 억제한 반면 IL-6 생성 억제에는 영향을 나타내지 않았다. 이러한 염증 매개인자 억제 효능은 SPPE가 PPWE보다 더 뛰어나게 억제하는 것을 확인하였다. 따라서 감껍질 추출물은 아토피 피부염 증상 개선과 염증관련 질환 치료를 위한 기능성 천연물 소재로 유용하게 활용될 수 있을 것으로 판단된다. This study aimed to investigate the anti-atopic effect of hot water (PPWE) and supercritical-carbon dioxide fluid extract of persimmon peels (SPPE) on atopic dermatitis (AD)-like skin lesions in hairless mice. Histological analyses demonstrated that SPPE treatment more strongly inhibited the dermal infiltration of inflammatory cells in AD-like skin lesions than that by PPWE. Compared to PPWE, SPPE significantly decreased the dermatitis clinical score and the epidermal thickness and potently suppressed serum IgE and interleukin (IL)-4 production in hairless mice with AD. Furthermore, compared to PPWE, SPPE potently inhibited the production of nitric oxide, prostaglandin E₂, and proinflammatory cytokines such as IL-6 and IL-1β in lipopolysaccharide-stimulated RAW264.7 macrophages. These results suggested that SPPE exhibited anti-atopic dermatitis activity via the regulation of inflammatory responses.

중국 덕주 지역의 구순구개열 의료 봉사 활동 보고 및 치험례 발표

이원덕,이부규,최진영,김종렬,오용석,민병일,김명진,Lee, Won-Deok,Lee, Bu-Kyu,Cho, Jin-Young,Kim, Jong-Ryul,Oh, Yong-Seok,Min, Byoung-Il,Kim, Myung-Jin 대한악안면성형재건외과학회 2009 Maxillofacial Plastic Reconstructive Surgery Vol.31 No.5

Il Woong Cleft lip and palate foundation was founded in 1968 by Professor emeritus Byoung-Il Min. Since then the foundation has operated numerous cleft lip and palate patients not only in Korea but also in under-developed countries such as Vietnam, China, and Cambodia. In December 2005, the foundation was allowed as an incorporated association by Ministry of Foreign affairs and Trade, so that it could have official status. From March 6th 2009 to March 14th 2009, we conductp,d charity cleft lip and palate operations of 23 patients in areas of Deozhou, China. Hereby we present the results of operations.

Corrosion and Oxidation Resistance Behaviors of Ta-Containing Low Alloying Zirconium

Il‑Hyun Kim,Yang‑Il Jung,Byoung‑Kwon Choi,Hyun‑Gil Kim,Jae‑Il Jang 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.8

Zirconium alloys are widely used to fabricate nuclear fuel claddings, and thus is desirable to improve the resistance of suchalloys to corrosion and structural instability. In this study, Ta was used as an alloying element to improve the corrosion andoxidation resistance of zirconium alloys. The model alloy (TaZL) contained 0.03 wt% Ta and other elements with a proportionof less than 1 wt% in total (0.1 wt% Nb, 0.4 wt% Fe, 0.2 wt% Cr) in a zirconium base. The corrosion test involving pressurizedwater at 360 °C and oxidation test involving steam at 1200 °C indicated that TaZL exhibited the lowest weight gains amongthose of compared conventional and advanced Zr alloys. The corrosion and oxidation resistances of TaZL were respectivelyimproved by 4 and 1.5 times compared to the corresponding values of Zircaloy-4. The microstructures of the oxide formedon TaZL were columnar along the oxide growth direction and did not change from columnar to equiaxed, which resulted inthe high resistance of the alloy to corrosion and oxidation.

Soybean Fermented with Bacillus amyloliquefaciens (Cheonggukjang) Ameliorates Atopic Dermatitis-Like Skin Lesion in Mice by Suppressing Infiltration of Mast Cells and Production of IL-31 Cytokine

( Byoung Ok Cho ),( Jae Young Shin ),( Ji-su Kim ),( Denis Nchang Che ),( Hyun Ju Kang ),( Do-youn Jeong ),( Seon Il Jang ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 Journal of microbiology and biotechnology Vol.29 No.5

The present study was conducted with the aim to investigate the ameliorative effects of a new soybean product (cheonggukjang) fermented with Bacillus amyloliquefaciens SCGB1 (SFBA) in atopic dermatitis (AD) mouse model. Visual evaluation of AD induction in the mice indicated the remarkable control of SFBA in reducing the pathological severity of AD-like skin lesions reported as the SCORAD score of AD clinical symptoms. The results revealed that SFBA reduced dorsal skin and epidermal thickness to a similar extent with prednisolone. Further analysis revealed the dominance of SFBA in restraining mast cell infiltration in the dermis; immunoglobulin-E expression in serum; and TH2 IL-4 cytokine and itch-related IL-31 cytokine in the mice skin and serum. SFBA also suppressed scratching behaviours in mice induced by compound 48/80. Further histological findings also revealed the alleviation of collagen fiber deposition in dermal skin of the AD mice model. These actions of SFBA were examined to be mediated by its suppression of the phosphorylation activation of key signalling molecules such as NF-κB and MAPK responsible for the induction of cytokine production. Thus, SFBA can be considered as a promising functional food for managing clinical, histological and immunological spectra associated with AD.

Luteolin and apigenin inhibits itch-related IL-31 and IL-33 cytokines in mouse astrocytes

Seon Il Jang,Denis Nchang Che,Byoung Ok Cho,Jae Young Shin,Hyun Ju Kang,Ji-su Kim,Young-Soo Kim 한국식품영양과학회 2019 한국식품영양과학회 학술대회발표집 Vol.2019 No.10

포도가지 추출물의 산화방지, 항염증 및 항가려움 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),체 데니스 창(Denis Nchang Che),김상준(Sang Jun Kim),유철(Cheol Ryu),장선일(Seon Il Jang) 한국식품과학회 2016 한국식품과학회지 Vol.48 No.6

본 연구에서는 우리나라에서 가장 많이 재배되고 있는 캠벨어얼리 포도 품종에서 포도가지를 대상으로 산화방지, 항염증 및 항가려움증 효과를 검증하고 활성물질을 나타내는 지표물질을 추적 조사하였다. 그 결과 포도가지 추출물의 총 폴리페놀과 총 플라보노이드 함량은 각각 201.42±4.16과 11.85±0.44 mg GAE/g으로 조사되었다. 또한 캠벨어얼리 포도가지 추출물의 ABTS와 DPPH 라디칼 소거 활성은 각각 45.60±0.09 (IC50)과 299.13±0.22(IC<SUB>50</SUB>)으로 나타나 산화방지 활성이 우수하였다. 게다가 캠벨어얼리 포도가지 추출물은 지방질다당류로 활성화된 RAW 264.7 세포에서 전염증성 매개물인 산화질소와 프로스타글란딘 E₂를 iNOS와 COX-2 분자 발현 억제를 통하여 억제하였고, 전염증성 사이토카인인 인터류킨-1베타와 인터류킨-6를 농도 의존적으로 억제하는 효능이 있었다. 더욱이 phorbol 12-myristate 13-acetate (PMA)와 calcium ionophore A23187로 활성화된 인간 유래 비만세포인 HMC-1 세포에서 종양괴사인자-알파와 인터류킨-6를 농도 의존적으로 억제하는 효능이 있었다. 마지막으로 Compound 48/80으로 유도되는 마우스 가려움증을 캠벨어얼리 포도가지 추출물은 효과적으로 억제하였다. 이러한 캠벨어얼리 추출물에서 활성을 나타내는 물질을 추적한 결과 레스베라트롤의 함량이 높게 검출되었다. 그러므로 본 연구의 결과를 종합해 볼 때 캠벨어얼리 포도가지 추출물은 아토피 질환에서 나타나는 염증과 가려움증을 효과적으로 제어할 수 있는 효과적인 소재임을 제시하였다. This study was designed to investigate the antioxidant activities of the ethanol extracts (GBE) of grape branches (Campbell Early). The total polyphenol and flavonoid content of GBE was 201.42±4.16 and 11.85±0.44 mg GAE/g, respectively. The antioxidant activity of GBE was measured using the ABTS and DPPH assays, and the IC<SUB>50</SUB> values were 45.60±0.09 and 299.13±0.22, respectively. GBE inhibited the production of pro-inflammatory mediators (NO, iNOS, PGE₂, COX-2, IL-1β, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. Moreover, GBE treatment significantly suppressed the production of TNF-α and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. Furthermore, the administration of GBE markedly inhibited the scratching behavior induced by the compound 48/80 in ICR mice. These results suggested that GBE has potential as a therapeutic agent against inflammation and itch-related skin diseases.

Rosmarinic acid와 luteolin의 항염증에 대한 상승효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),방숭주(Chong Zhou Fang),하혜옥(Hye Ok Ha),김상준(Sang Jun Kim),정승일(Seung Il Jeong),장선일(Seon Il Jang) 한국식품과학회 2015 한국식품과학회지 Vol.47 No.1

본 연구에서는 들깨 유래 기능성 물질인 rosmarinic acid (RA)와 luteolin이 RAW264.7 세포에서 항염증작용에 대한 상승 효과가 있는지 알아보고자 하였다. 그 결과 RAW264.7 세포에 RA (50 μM)와 luteolin (1 μM)을 동시에 처리하였을 경우 염증 매개 인자인 NO, iNOS, PGE2, COX-2의 생성을 RA (100 μM)와 luteolin (2 μM)을 각각 처리하였을 때 보다 더 뛰어나게 억제하였다. 또한 RA (50 μM)와 luteolin (1 μM)을 동시에 처리하였을 경우 TNF-α, IL-6, IL-1β 같은 염증성 사이토카인의 생성량을 RA (100 μM)와 luteolin (2 μM)을 각각 처리하였을 때 보다 더 뛰어나게 억제하는 것을 확인하였다. 그리고 RA (50 μM)와 luteolin (1 μM)을 동시에 처리하였을 경우 RA (100 μM)와 luteolin (2 μM)을 각각 처리하였을 때 보다 NF-κB의 subunit인 p65의 translocation과 IκB-α의 degradation을 더 뛰어나게 억제하는 것을 볼 수 있어 두 화합물 간의 상승작용이 뚜렷함을 확인 할 수 있었고, RA와 luteolin 두 화합물을 동시에 처리할 경우 염증관련 질환 치료에 유용하게 활용될 수 있을 것으로 판단된다. The aim of this study was to investigate the synergistic anti-inflammatory effect of rosmarinic acid (RA) and luteolin from perilla (Perilla frutescens L.) leaves in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. A combination of RA and luteolin more strongly inhibited the production of nitric oxide (NO), inducible NOS (iNOS), prostaglandin E2 (PGE2), and COX-2 than higher concentrations of RA or luteolin alone in LPS-stimulated RAW264.7 macrophages. The combined RA and luteolin synergistically inhibited the production of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), in LPS-stimulated RAW264.7 macrophages. Furthermore, combined RA and luteolin more strongly suppressed NF-κB activation than RA or luteolin alone, by inhibiting the degradation of inhibitor of NF-κB (IκB)-α and nuclear translocation of the p65 subunit of NF-κB in LPS-stimulated RAW264.7 macrophages. Collectively, these results suggest that RA and luteolin in combination exhibit synergistic effects in suppression of LPS-induced inflammation in RAW264.7 macrophages.

코디세핀이 마우스 복강 대식세포에서 전염증성 사이토카인의 생성에 미치는 영향

서민정(Min-Jeong Seo),강병원(Byoung-Won Kang),김민정(Min-Jeong Kim),이혜현(Hye-Hyeon Lee),서권일(Kwon-il Seo),김광혁(Kwang-Hyuk Kim),정영기(Yong-Kee Jeong) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.1

본 연구는 동충하초(Cordyces militaris) 유래의 기능성 물질인 코디세핀의 면역활성을 검증하기 위하여 C57BL6 마우스 복강 대식세포를 이용하여 코디세핀이 대식세포의 활성화에 미치는 영향에 대하여 시험하였다. 그 결과 LPS에 의해 유도된 마우스 복강세포는 코디세핀의 작용에 의해 IL-1β, IL-12, TNF-α의 염증성 사이토카인의 생성이 증대되어 초기 염증매개 반응을 유도하여 선천면역반응의 활성화와 그리고 면역작용에 있어 후기 적응면역의 전환으로의 T 림프구의 활성화가 예상된다. 또한 IL-6의 생성증대로 활성화된 T 림프구에 의해 B 림프구의 항체생성반응을 매개하는 면역반응도 상승할 것으로 사료된다. 그리고 대식세포에 의한 염증반응에서 염증매개인자인 NO와 H₂O₂의 생성을 증대시킴에 따라 대식세포의 독성작용을 활성화시켜 염증반응을 효과적으로 유도할 것으로 보이며, 또한 H₂O₂의 후기 생성을 저해하였는데 이는 염증반응에 유도될 수 있는 세포의 손상으로부터 세포를 보호할 수 있을 것으로 사료된다. 따라서 코디세핀은 외부인자로부터 염증매개성 면역반응의 증강작용을 나타내는 것으로 사료된다. The effect of cordycepin purified from Cordyceps militaris on macrophage activation was investigated in peritoneal macrophages isolated from C57BL6 mice. Lipopolysaccharide-induced mouse peritoneal cells showed that cordycepin treatment increased the expression of the inflammatory cytokines interleukin (IL)-1β, IL-12, and tumor necrosis factor-α (TNF-α), leading to early inflammation-mediated reactions, the activation of immunological responses, and T lymphocyte activation. T lymphocytes, activated by a greater production of IL-6, resulted in antibody-generating immune reactions, suggesting that cordycepin was effective at inducing immunological responses. Consistent with the increase in the inflammation-mediating factors including nitric oxide (NO) and hydrogen peroxide (H₂O₂), the toxic response of macrophages was activated and effectively induced inflammation. These findings demonstrate that cordycepin is involved in reducing cell injury provoked by inflammatory reactions. Therefore, these results suggest that cordycepin treatment of mouse peritoneal cells induces inflammation-mediated immunological responses and immunostimulation.

구강내에서 재광화용액 "R"의 법랑질 초기 우식병소에 대한 재광화의 정량적 평가

김명은,정일영,금기연,이찬영,노병덕 大韓齒科保存學會 2002 Restorative Dentistry & Endodontics Vol.27 No.2

Dental caries is a chronic disease that causes the destruction of tooth structure by the interaction of plaque bacteria, food debris, and saliva. There has been attempts to induce remineralization by supersaturating the intra-oral environment around the surface enamel, where there is incipient caries. In this study, supersaturated remineralized solution "R" was applied to specimens with incipient enamel caries, and the quantitative ananlysis of remineralization was evaluated using microradiography. Thirty subjects volunteered to participate in this study. Removable appliances were constructed for the subjects. and the enamel specimen with incipient caries were embedded in the appliances. The subjects wore the intra-oral appliance for 15 days except while eating and sleeping. The removable appliance were soaked in supersaturated solution "R", saline, or Senstime® to expose the specimen to those solutions three times a day, 5 minutes each time. After 15 days, microradiography was retaken to compare and evaluate remineralization. The results were as the following: 1. The ratio of remineralized area to demineralized area was significantly higher in the supersaturated solution "R" and Senstime® than in the saline (p<0.05) 2. Remineralization in the supersaturated buffer solution "R" occurred in the significantly deeper parts of the tooth, compared to the Senstime® group containing high concentration of fluoride.(p<0.05) As in the above results, the remineralization effect of remineralized buffer solution "R" on incipient enamel caries has been proven. For clinical utilization, further studies on soft tissue reaction and the effect on dentin and cementum are necessary. In conclusion compared to commercially available fluoride solution, remineralization solution "R" showed better remineralization effect on early enamel caries lesion. so it is considered as effecient solution for clinical application