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>

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.

Anti-inflammatory Activity of 1-docosanoyl Cafferate Isolated from <I>Rhus verniciflua</I> in LPS-stimulated BV2 Microglial Cells

Jae-Won Lee,Il-Young Cheong,Hae-Sung Kim,Jae Jun Lee,Yong-Suk Lee,Yong-Soo Kwon,Myong-Jo Kim,Hee Jae Lee,Sung-Soo Kim,Wanjoo Chun 대한생리학회-대한약리학회 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.1

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as protection of neuronal cells against excitotoxicity, the biological activity of 1-docosanoyl cafferate (DC) has not been examined. The objective of the present study was to evaluate the anti-inflammatory effects of DC, isolated from the stem bark of <i>Rhus verniciflua</i>, on lipopoly</I>saccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of cells with DC significantly attenuated LPS-induced NO production, and mRNA and protein expression of iNOS in a concentration- dependent manner. DC also significantly suppressed LPS-induced release of cytokines such as TNF-Ձ and IL-1Ղ. Consistent with the decrease in cytokine release, DC dose-dependently and significantly attenuated LPS-induced mRNA expression of these cytokines. Furthermore, DC significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB induced by LPS stimulation was significantly suppressed with DC pretreatment. Taken together, the present study suggests that DC exerts its anti-inflammatory activity through the suppression of NF-kB translocation to the nucleus.

Anti-inflammatory Activity of 1-docosanoyl Cafferate Isolated from Rhus verniciflua in LPS-stimulated BV2 Microglial Cells

Lee, Jae-Won,Cheong, Il-Young,Kim, Hae-Sung,Lee, Jae-Jun,Lee, Yong-Suk,Kwon, Yong-Soo,Kim, Myong-Jo,Lee, Hee-Jae,Kim, Sung-Soo,Chun, Wan-Joo The Korean Society of Pharmacology 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.1

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as protection of neuronal cells against excitotoxicity, the biological activity of 1-docosanoyl cafferate (DC) has not been examined. The objective of the present study was to evaluate the anti-inflammatory effects of DC, isolated from the stem bark of Rhus verniciflua, on lipopoly-saccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of cells with DC significantly attenuated LPS-induced NO production, and mRNA and protein expression of iNOS in a concentration-dependent manner. DC also significantly suppressed LPS-induced release of cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. Consistent with the decrease in cytokine release, DC dose-dependently and significantly attenuated LPS-induced mRNA expression of these cytokines. Furthermore, DC significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB induced by LPS stimulation was significantly suppressed with DC pretreatment. Taken together, the present study suggests that DC exerts its anti-inflammatory activity through the suppression of NF-kB translocation to the nucleus.

Effects of Melatonin and Its Underlying Mechanism on Ethanol-Stimulated Senescence and Osteoclastic Differentiation in Human Periodontal Ligament Cells and Cementoblasts

Bae, Won-Jung,Park, Jae Suh,Kang, Soo-Kyung,Kwon, Il-Keun,Kim, Eun-Cheol MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.6

<P>The present study evaluated the protective effects of melatonin in ethanol (EtOH)-induced senescence and osteoclastic differentiation in human periodontal ligament cells (HPDLCs) and cementoblasts and the underlying mechanism. EtOH increased senescence activity, levels of reactive oxygen species (ROS) and the expression of cell cycle regulators (p53, p21 and p16) and senescence-associated secretory phenotype (<I>SASP</I>) genes (interleukin [IL]-1β, IL-6, IL-8 and tumor necrosis factor-α) in HPDLCs and cementoblasts. Melatonin inhibited EtOH-induced senescence and the production of ROS as well as the increased expression of cell cycle regulators and SASP genes. However, it recovered EtOH-suppressed osteoblastic/cementoblastic differentiation, as evidenced by alkaline phosphatase activity, alizarin staining and mRNA expression levels of Runt-related transcription factor 2 (Runx2) and osteoblastic and cementoblastic markers (glucose transporter 1 and cementum-derived protein-32) in HPDLCs and cementoblasts. Moreover, it inhibited EtOH-induced osteoclastic differentiation in mouse bone marrow–derived macrophages (BMMs). Inhibition of protein never in mitosis gene A interacting-1 (PIN1) by juglone or small interfering RNA reversed the effects of melatonin on EtOH-mediated senescence as well as osteoblastic and osteoclastic differentiation. Melatonin blocked EtOH-induced activation of mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and Nuclear factor of activated T-cells (NFAT) c-1 pathways, which was reversed by inhibition of PIN1. This is the first study to show the protective effects of melatonin on senescence-like phenotypes and osteoclastic differentiation induced by oxidative stress in HPDLCs and cementoblasts through the PIN1 pathway.</P>

금은화(金銀花) 및 금은화전초(金銀花全草)가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향

이동언,이재령,김영우,권영규,변성희,신상우,서성일,권택규,변준석,김상찬,Lee, Dong-Eun,Lee, Jae-Ryung,Kim, Young-Woo,Kwon, Young-Kyu,Byun, Sung-Hui,Shin, Sang-Woo,Suh, Seong-Il,Kwon, Taeg-Kyu,Byun, Joon-Seok,Kim, Sang-Chan 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.2

Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.

큰느타리버섯(Pleurotus eryngii) 조다당체의 면역세포 활성화 효과

강혜인(Hye-In Kang),김재용(Jae-Yong Kim),문광덕(Kwang-Deog Moon),서권일(Kwon-Il Seo),조영숙(Young-Sook Cho),이상대(Sang-Dae Lee),이성태(Sung-Tae Yee) 한국식품영양과학회 2004 한국식품영양과학회지 Vol.33 No.7

큰느타리버섯의 기능성 식품으로서 활용도를 높이기 위해 동결 건조된 자실체에서 분리한 조다당체 추출물이 면역세포 활성에 미치는 효과를 조사한 결과는 다음과 같다. 조다당체 추출물은 300 및 1,000 ㎍/mL 농도에서 비장세포의 증식을 유도하였으며, 이때 비장세포는 IL-6와 IFN-γ 분비를 유도하는 것으로 나타났다. 조다당체 추출물은 농도 의존적으로 B세포의 증식을 유도하였으며, 특히 100 ㎍/mL 농도 이상에서는 B세포의 증식이 현저히 증가하는 것으로 나타났다. 그리고 조다당체 추출물 1,000 ㎍/mL 농도에서 B세포가 생산하는 IgG1, IgG2a, IgG3의 분비량이 현저히 증가하였다. 또한 농도 의존적으로 대식세포주의 일산화질소 생산을 유도하였으며, 대식세포가 분비하는 IL-6, TNF-α, GM-CSF의 생산도 현저히 증가하는 것을 확인할 수 있었다. The objective of the current study was to determine the effects of the crude polysaccharide isolated from fruit body of Pleurotus eryngii on mouse splenocytes, B cells, and macrophages in vitro. The crude poly-saccharides directly induced the proliferation of spleen cells in a dose-dependent manner and increased IL-6 and IFN-γ synthesis. The crude polysaccharides also increased the proliferation of B cells in a dose-dependent manner. The production of immunoglobulin G1, G2a and IgG3 in the presence of the crude polysaccharides was increased progressively in the culture supernatant. When the crude polysaccharide were used in macrophage cell line (RAW264.7) stimulation, there were marked induction of NO synthesis in a dose-dependent manner and IL-6, TNF-γ and GM-CSF synthesis. These results suggest that the crude polysaccharide isolated from fruit body of Pleurotus eryngii seem to act as a potent immunomodulator causing augmentation of immune cell activity, and thus could be used as a biological response modifier having possible therapeutic effects against immunological disorders, without any side effects.

만성폐쇄성폐질환의 중증도와 폐고혈압 및 폐성심으로 진행과의 상관관계

김형호,박철진,이준,장광표,하성일,이재록,하재화,권세훈,권용운,윤성호,이승일 朝鮮大學校 附設 醫學硏究所 2007 The Medical Journal of Chosun University Vol.32 No.2

Background: From many previous studies, Pulmonary hypertension is the known independent predictive factor of the mortality in COPD. Also pulmonary hypertension is the major cardiovascular complication of COPD and is associated with the progression to cor pulmonale and poor prognosis. Author want to analyze the correlation between pulmonary hypertension and the severity of COPD which are classified by forced expiratory volume in one second, and the extent of progression to corpulmonale. Methods: Retrospectively we investigated the medical records of 118 patients with COPD who had pulmonary function test and echocardiogaphy more than one times during one-year follow-up (from June, 2005 to May, 2006) at respiratory division in chosun university hospital, and then 50 patients were enrolled in this study. We classified the severity from FEVl in pulmonary function test based on the GOLD guideline, also this was comparably analyzed with RVSP, RVIDd, Visual Grading from echocardiography. Results: 16 patients out of 50 were classified as moderate severity, 25 patients were severe, and 9 patients were very severe group. RVSP was higher in more severe groups than less severe groups but when it comes to pulmonary hypertension that RVSP is over 35 mmHg, there was no valid difference lies in those groups. As FEVl decreases RVSP and RVIDd increases, and observed relationship between RVSP which was classified as below 35 mm and above 35 mm groups and visual grading which was classified as normal and dilatated groups revealed valid correlation, Conclusion: As pulmonary function decreases, progression to pulmonary hypertension and cor pulmonale increases but there was no remarkable difference of prevalence in above moderate severity groups. 연구배경 폐고혈압은 이전의 많은 연구에서 만성폐쇄성폐질환에서 독립적인 사망의 예측인자로 알려져 있다. 또한 폐고혈압은 만성폐쇄성폐질환의 주요한 심혈관계 합병증이며, 폐성심으로의 진행 및 불량한 예후와도 관련되어 있다. 이에 저자는 폐고혈압과 1초간 노력성호기량으로 분류되는 만성폐쇄성폐질환의 중증도 및 폐성심으로의 진행 정도를 비교 분석하여 이들의 상관관계를 밝혀보고자 한다. 방법 2005년 6월부터 2006년 5월까지 1년 동안 본 병원 호흡기 내과에서 폐기능검사와 심장초음파 검사를 각각 1회 이상 시행한 적이 있는 118명에 한하여 의무기록을 후향적으로 조사하여 이 중에서 50명을 대상으로 하였다. 폐기능검사 시행 결과 얻은 1초간 노력성호기량을 바탕으로 GOLD guideline에 따라 중증도를 분류하였으며 이를 심초음파 시행 결과 얻은 우심실수축기압, 확장기말 우심실내부간격, 시각등급과 비교분석하였다. 결과 대상 환자 50명중 16명은 중등증, 25명은 중증, 9명은 최고중증 그룹으로 분류되었다. 우심실수축기압은 중증도가 높은 그룹에서 낮은 그룹에 비해 더 높게 나타났으나 폐고혈압에 해당하는 우심실수축기압이 35 mmHg이상인 환자에 있어사는 각 그룹간에 유의한 차이를 보이지 않았으며, 확장기말 우심실내부간격, 시각등급 또한 중증도와 유의한 차이를 보이지 안항ㅆ다. 1초간 노력성호기량이 감소함에 따라서는 우심실수축기압, 시각등급은 증가하였으며 우심실수축기압을 35mmHg 미만과 이상인 그룹으로, 시각등급을 정상과 확장이 있는 그룹으로 분류하여 비교한 결과에서는 유의한 상관관계를 나타냈다. 결론 폐기능이 감소할수록 페고혈압 및 폐성심으로의 진행이 증가하였으나 폐기능검사에서 중등도 이상의 그룹에서 유병률의 차이는 크지 않았다.

A genome-wide by PM₁₀ interaction study identifies novel loci for lung function near <i>BICD1</i> and <i>IL1RN-IL1F10</i> genes in Korean adults

Kim, Hyun-Jin,Seo, Yong-Seok,Sung, Joohon,Chae, Jeesoo,Yun, Jae Moon,Kwon, Hyuktae,Cho, Belong,Kim, Jong-Il,Park, Jin-Ho Elsevier 2020 CHEMOSPHERE - Vol.245 No.-

<P><B>Abstract</B></P> <P>Although several genome-wide interaction studies (GWIS) have been performed in specific European populations to understand the missing link between genetic and environmental factors for lung function, GWIS of Asian samples remain rare. Therefore, we performed a GWIS of exposure to air pollution to identify loci for lung function in Korean adult men. A total of 1826 adult men recruited from two health check-up centers were included in the analysis and the annual mean concentrations of ambient particulate matter with an aerodynamic diameter ≤10 μm (PM<SUB>10</SUB>) were used. In case of forced vital capacity (FVC), one SNP (rs12312730) that passed our genome-wide threshold of <I>p</I>int < 1 × 10–5 was detected in the intronic region of the <I>BICD1</I> gene on chromosome 12. In addition, we found two variants (rs6743376 and rs17042888) located near the <I>IL1RN-IL1F10</I> gene that were involved in the inflammatory response and associated with decreased FVC via interaction with PM<SUB>10</SUB> exposure. A stratified association analysis according to these SNP genotypes showed that PM<SUB>10</SUB> concentrations in subjects with one or two of the risk alleles, compared with those with the non-risk allele, were significantly correlated with a reduction in FVC. This pattern was replicated in another 892 Korean adult samples. The current study reports the first GWIS discovery in an Asian population: the <I>BICD1</I> and <I>IL1RN-IL1F10</I> genes may contribute to the decrease in FVC levels by interacting with PM<SUB>10</SUB> exposure.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Significant interactions between <I>BICD1 or IL1RN-IL1F10</I> and PM<SUB>10</SUB> for FVC were found. </LI> <LI> The several SNPs in these genes were more susceptible to FVC decline by PM<SUB>10</SUB>. </LI> <LI> For FVC, these interaction effects were reproducible in another sample. </LI> </UL> </P>

큰느타리버섯 균사체로 제조한 발효두부 추출물의 면역 활성

이상원(Sang-Won Lee),강종우(Jong-Woo Kang),김재용(Jae-Yong Kim),박경욱(Kyung-Wuk Park),박석규(Seok-Kyu Park),주옥수(Ok-Soo Joo),이성태(Sung-Tae Yee),서권일(Kwon-Il Seo) 한국식품영양과학회 2010 한국식품영양과학회지 Vol.39 No.1

두부의 기능성 및 저장성을 향상시킬 목적으로 큰느타리버섯 균사체를 이용한 발효두부를 제조하여 물과 메탄올로 추출하여 면역세포 활성에 미치는 효과를 조사하였다. 큰느타리버섯 균사체를 배양하기 위한 최적 배지는 PD broth 배지인 것을 확인하였으며, 큰타리버섯 균사체를 이용한 두부의 최적 발효기간은 7일 정도가 적당하였다. 큰느타리버섯 균사체를 이용하여 발효한 두부의 물 및 메탄올추출물은 0.01 ㎍/mL 농도 이상에서 비장세포의 증식을 유도하였으며, 이들 추출물은 IL-6, IFN-γ 분비를 유도하는 것으로 나타났다. 발효두부 물 추출물은 대조군에 비해 대식세포의 일산화질소 생산을 1 ㎍/mL 농도 이상에서 유의적으로 증가시키는 것을 알 수 있었으며, 메탄올 추출물은 10 ㎍/mL 농도 이상에서 그 생산을 증가시켰다. 발효두부 추출물들은 대식세포가 분비하는 IL-6, TNF-α, IL-1β 및 GM-CSF 분비량을 유의하게 증가시켰다. 따라서 큰느타리버섯 균사체로 발효한 두부는 기능성 두부로 개발이 가능하리라 생각된다. In order to improve the functional benefits and storage properties of soybean tofu, fermented tofu was developed using Pleurotus eryngii mycelia. The immune activities of water and methanol extracts of the tofu were investigated. The optimal medium for the growth of Pleurotus eryngii mycelia was PD broth medium and the optimal fermentation period for the tofu was 7 days. The water and methanol extracts of the fermented tofu induced the proliferation of spleen cells at above 0.01 ㎍/mL. The water extract increased IL-2, IFN-γ production, while the methanol extract increased IFN-γ synthesis. The water and methanol extracts of the fermented tofu induced the NO production in RAW264.7 macrophage cells at above 1 ㎍/mL and above 10 ㎍/mL concentration, respectively. The extracts also significantly increased the production of IL-6, TNF-α, IL-1β and GM-CSF in the cells. These results suggest that the tofu fermented with Pleurotus eryngii mycelia could be developed as a functional tofu.