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>

Effective Microorganism Substance (EM-S) Reduces Development and Aggravation of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

( Kwang Hyun Park ),( Seung Ii Jeong ),( Ji Ye Mok ),( Jung Keun Cho ),( Ji Min Park ),( In Hwa Jeon ),( Hyeon Soo Kim ),( Seon Il Jang ) 한국응용생명화학회 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.2

In a previous study, our group showed that the effective microorganism substance (EM-S) produced by fermentation of medicinal plants with effective microorganisms has an anti-inflammatory effect on atopic dermatitis-like lesions in NC/Nga mice. However, the possible anti-inflammatory effect and skin barrier function of EM-S for inflammatory cell infiltration, Interleukin-4 (IL-4) production, C-C chemokine receptor 10 (CCR10), and filaggrin (FLG) expression were not reported. Therefore, effects of EM-S on the development of atopic dermatitislike skin lesions in NC/Nga mice were evaluated. Efficacy of EM-S was judged by measurement of scratching behavior, T-cell subset infiltration, cytokine production, and FLG expression. Topical application of EM-S significantly reduced scratching behavior in NC/Nga mice caused by house dust mite antigen (Dermatophagoides farinse extract, DfE) sensitization. IL-4 production and CD4+ and CD45+ cell infiltrations were significantly reduced by EM-S. CCR10 expression was also significantly inhibited by EM-S. EM-S treatment also increased the level of FLG reduced by DfE sensitization. These results demonstrate EM-S, when applied topically, may be an effective substance for management of atopic dermatitis patients.

Fermented Herbal Formulas KIOM-MA128 Ameliorate IL-6-Induced Intestinal Barrier Dysfunction in Colon Cancer Cell Line

Park, Kwang Il,Kim, Dong Gun,Lee, Bo Hyoung,Ma, Jin Yeul Hindawi Publishing Corporation 2016 MEDIATORS OF INFLAMMATION Vol.2016 No.-

<P>Inflammatory bowel disease (IBD) comprises Crohn's disease (CD) and ulcerative colitis (UC). IBD increases the risk of colorectal cancer (CRC), depending on the extent and duration of intestinal inflammation. Increased IL-6 expression has been reported in IBD patients, which may be associated with intestinal barrier function through discontinuous tight junction (TJ). KIOM-MA is a specific agent for allergic diseases and cancer, and it is composed of several plants; these herbs have been used in traditional oriental medicine. We fermented KIOM-MA, the product of KIOM-MA128, using probiotics to improve the therapeutic efficacy via the absorption and bioavailability of the active ingredients. In this study, we demonstrated that KIOM-MA/MA128 exhibited anticolitis effects via the modulation of TJ protein. Interleukin-6 resulted in a dose-dependent decrease in the TER and an increase in the FITC-dextran permeability; however, pretreatment with 400 <I>µ</I>g/ml KIOM-MA/MA128 resulted in a significant increase in the TER and a decrease in the FITC-dextran permeability via IL-6 induction. Furthermore, protein and mRNA TJ levels remained stable after pretreatment with 400 <I>µ</I>g/ml KIOM-MA/MA128. Moreover, KIOM-MA/MA128 suppressed the expression of PLC<I>γ</I>1 and PKC. Taken together, these findings suggest novel information and clue of the anticolitis effects of KIOM-MA128 via regulation of tight junction.</P>

Amelioration of inflammatory responses by <i>Socheongryong-Tang</i> , a traditional herbal medicine, in RAW 264.7 cells and rats

Park, Sang Mi,Lee, Tae Hoon,Zhao, Rongjie,Kim, Youn Sook,Jung, Ji Yun,Park, Chung A.,Jegal, Kyung Hwan,Ku, Sae Kwang,Kim, Jae Kwang,Lee, Chul Won,Kim, Young Woo,Cho, Il Je,An, Won G.,Kim, Sang Chan D.A. Spandidos 2018 International journal of molecular medicine Vol.41 No.5

<P>Socheongryong-Tang (SCRT) is a natural medicine prescription that has been mainly used in East Asia for the treatment of inflammatory disorders, including asthma and allergic rhinitis. The present study evaluated the anti-inflammatory effects of SCRT on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and in a rat model of carrageenan (CA)-induced paw edema. Levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>) in the culture supernatant were quantified and nitric oxide (NO) production was monitored. In addition, the effect of SCRT on the protein expression of nuclear factor-κB (NF-κB), mitogen-activated protein kinases (MAPKs), inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was assessed by western blot analysis. Furthermore, the effects of SCRT on acute inflammation <I>in vivo</I> and changes in the histomorphometry and histopathology of paw skin were observed using CA-treated rats. SCRT (1 mg/ml) inhibited the LPS-induced changes in the protein expression of NF-κB, JNK, ERK1/2, iNOS and COX-2, as well as the production of NO, PGE<SUB>2</SUB> and cytokines. In the rat paw edema assay, administration of 1 g/kg of lyophilized powder obtained from the aqueous extracts of SCRT for 3 consecutive days inhibited the CA-induced increases in skin thickness, mast cell degranulation, and infiltration of inflammatory cells in the ventral and dorsal pedis skin within 4 h. These results demonstrated that SCRT exerts its anti-inflammatory activities in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, including PGE<SUB>2</SUB>, NO and cytokines, via suppression of the NF-κB and JNK and ERK1/2 signaling pathways. In addition, the data of the CA-induced paw edema indicated an anti-edema effect of SCRT. SCRT (1 g/kg) reduced acute edematous inflammation through inhibition of mast cell degranulation and infiltration of inflammatory cells. Therefore, the present study provided scientific evidence for the anti-inflammatory activities of SCRT as well as the underlying mechanisms.</P>

Regulation of Proinflammatory Mediators via NF- <i><i>κ</i></i> B and p38 MAPK-Dependent Mechanisms in RAW 264.7 Macrophages by Polyphenol Components Isolated from Korea <i>Lonicera japonica THUNB</i>

Park, Kwang-Il,Kang, Sang-Rim,Park, Hyeon-Soo,Lee, Do Hoon,Nagappan, Arulkumar,Kim, Jin A,Shin, Sung Chul,Kim, Eun Hee,Lee, Won Sup,Chung, Hyon-Jong,An, Su Jin,Kim, Gon Sup Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-

<P><I>Lonicera japonica THUNB.</I>, which abundantly contains polyphenols, has been used as a traditional medicine for thousands of years in East Asian countries because of the anti-inflammation properties. This study aimed to investigate the anti-inflammatory mechanism of polyphenol components isolated from Korea <I>L. japonica T.</I> by nuclear factor-kappaB (NF-<I><I>κ</I></I>B) and mitogen-activated protein kinases (MAPKs) pathway. Polyphenols significantly decreased lipopolysaccharide- (LPS-) induced mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as mRNA expression of tumor necrosis factor-alpha, interleukin- (IL-) 1<I><I>β</I></I>, and IL-6. Moreover, polyphenols inhibited nuclear translocation of NF-<I><I>κ</I></I>B p65, phosphorylation/degradation of the inhibitor of <I><I>κ</I></I>B, and phosphorylation of p38 MAPK, whereas the extracellular signal-regulated kinase and Janus N-terminal kinase were not affected. These results indicate that polyphenol components isolated from Korea <I>L. japonica T.</I> should have anti-inflammatory effect on LPS-stimulated RAW 264.7 cells through the decrease of proinflammatory mediators expression by suppressing NF-<I><I>κ</I></I>B and p38 MAPK activity.</P>

Effective Microorganism Substance (EM-S) Reduces Development and Aggravation of Atopic Dermatitis-like Skin Lesions in NC/Nga Mice

Park, Kwang-Hyun,Jeong, Seung-Il,Mok, Ji-Ye,Cho, Jung-Keun,Park, Ji-Min,Jeon, In-Hwa,Kim, Hyeon-Soo,Jang, Seon-Il The Korean Society for Applied Biological Chemistr 2011 Applied Biological Chemistry (Appl Biol Chem) Vol.54 No.2

In a previous study, our group showed that the effective microorganism substance (EM-S) produced by fermentation of medicinal plants with effective microorganisms has an antiinflammatory effect on atopic dermatitis-like lesions in NC/Nga mice. However, the possible antiinflammatory effect and skin barrier function of EM-S for inflammatory cell infiltration, Interleukin-4 (IL-4) production, C-C chemokine receptor 10 (CCR10), and filaggrin (FLG) expression were not reported. Therefore, effects of EM-S on the development of atopic dermatitislike skin lesions in NC/Nga mice were evaluated. Efficacy of EM-S was judged by measurement of scratching behavior, T-cell subset infiltration, cytokine production, and FLG expression. Topical application of EM-S significantly reduced scratching behavior in NC/Nga mice caused by house dust mite antigen (Dermatophagoides farinse extract, DfE) sensitization. IL-4 production and $CD4^+$ and $CD45^+$ cell infiltrations were significantly reduced by EM-S. CCR10 expression was also significantly inhibited by EM-S. EM-S treatment also increased the level of FLG reduced by DfE sensitization. These results demonstrate EM-S, when applied topically, may be an effective substance for management of atopic dermatitis patients.

Effect of Feed Selenium-lysine Supplementation on Milk Compositions and Serum Biochemical Indices in Saanen Dairy Goats

Tae-Il Kim,Dong-Hyun Lim,Tai-Young Hur,Seung-Min Ha,Hyun-Jong Kim,Seong-Min Park,Ji-Hoo Park,Sang-Bum Kim,Ji-Hwan Lee,Hyun-Joo Lim,Jeong-Sung Jung,Ha-Yeon Jeong,Jay Lee,Kwang-Seok Ki,Vijayakumar Mayak 경상대학교 농업생명과학연구원 2019 농업생명과학연구 Vol.53 No.4

An experiment was carried out to assess the effect of feed selenium-lysine (Se-Lys) supplementation on milk compositions and serum biochemical indices in Saanen dairy goats in Korea. A total of twelve 36 months old Saanen lactating dairy goats (47±6.21 kg) fed the similar dry matter intake twice a day at 2% of BW (DMI) (10.9% moisture of concentrate and 19% moisture of roughage), milk yield (2.5 kg/d) and parity (2) were randomly selected and subjected for the present study, divided into two groups with six goats in each group. The goats in the control group received rice hulls (10 g/ day) only, and did not receive Se-Lys; goats in the treatment group were fed 0.06 g of Se-Lys with 10 g of rice hulls every day before feeding roughage for six weeks. The milk sample was collected every week, and its compositions were analyzed. The results of the present study showed that there is no significantly increased milk production in Se-Lys treated group goats when compared with control group goats. But, Se-Lys treatment significantly increased the milk protein content (3.98±0.16%), fat (3.72±0.27%), lactose (4.07±0.14%), total solids (12.51±0.28%) and urea (14.42±1.45 mg/dl) content as compared to the control group goats (p<0.05). The somatic cell counts (207,740±28.81 cells/ml) were significantly lower in the Se-Lys treated group than in the control group (p<0.05). Also, the results of the current study showed that supplementation of Se-Lys were significantly decreased the blood biochemical indices of IL-6 (34.34±6.04 pg/ml), TNT-α (0.56±0.22 ng/ml), MDA (5.07±1.03 ng/ml), GPx-1 (9.07±5.17 ng/ml), sCD4 (2.64±1.02 ng/ml) and sCD8 (5.08±2.08 ng/ml) level when compared with without addition of Se-Lys group dairy goats (p<0.05). On the other hand, the selenoprotein P (1,580.18±127.62 ng/ml) level was significantly higher in Se-Lys supplemented group than in the control group (p<0.05). Based on the study results, it was concluded that feed Se-Lys supplementation may improve milk yield with positively improved protein, fat, lactose, total solids, urea content, and biochemical indices without negative effects on milk production traits.

Er:YAG 레이저와 Er,Cr: YSGG 레이저가 염증유발 마우스조직에 미치는 영향

박태일,이형석,이희종,채창훈,이영주,변광섭,홍순민,최미라,박준우,Park, Tae-Il,Lee, Hyung-Seok,Lee, Hee-Jong,Chae, Chang-Hoon,Lee, Young-Joo,Byeon, Kwang-Seob,Hong, Soon-Min,Choi, Mee-Ra,Park, Jun-Woo 대한악안면성형재건외과학회 2010 Maxillofacial Plastic Reconstructive Surgery Vol.32 No.5

Purpose: This study was performed to find out the effects of the Er:YAG laser (Key Laser) & Er,Cr:YSGG laser (Water Laser) on inflammatory tissues. Materials and Methods: It was performed on about 20 g, 6 weeks male ICR mouses. They were grouped into the control (negative), the inflammation induced 'control'(positive), Er,Cr:YSGG laser exposured group after inducing inflammation, Er:YAG lasere exposured group after inducing inflammation each 15 mouses. The mouses were applicated 0.5% DNFB 1 cc on ear skin twice a day for 4 days until symptom expression. After laser exposure, ear tissues were extracted and defined gene expression by RT-PCR. Then, tissue staining, lymphocytes observation, electromicroscophic laboratory were carried out. Results: Interleukin-$1{\beta}$ was expressed much less in the A-laser exposed group. Interleukin-$1{\beta}$ & Tumor Necrosis Factor-${\alpha}$ were expressed 7 times lesser in the A-laser exposed group. The number of Lymphocytes related to inflammation was decreased rapidly in the A-laser exposed group in vivo. he number of cavity recovered normal was a little bigger in the A-laser exposed group after 5 days Conclusion: The expression of IL-$1{\beta}$ & TNF-${\alpha}$, hitologic change, observation with electron microscope shows that Erbium laser exposure causes lesser inflammation with A-laser rather than B-laser.

Interleukin-6가 사람 골수기질세포의 Alkaline Phosphatase, Osteontin, Decorin 및 a1(1)-Collagen mRNA 발현에 미치는 영향

김동관,김철희,김기수,손광현,박승일 대한내분비학회 1996 Endocrinology and metabolism Vol.11 No.2

Background: Inter1eukin-6(IL-6) is known to be produced by osteoblastic cells and to have impartant role in regulation of bone remodelling, Most previous studies indicated that IL-6 bas a major role in stimulating osteoclastic resorption by increasing recruitment and proliferation of preosteoclasts. But its autocrine effect on osteoblastic cells has not been well established yet. Therefore, we studied the effects of IL-6 on messenger RNA (mRNA) expression of proteins that are characteristic of osteoblastic cells in human bone marrow stromal (osteoprogenitor) cells (hRMSC). Methods: The expression of mRNAs for alkaline phosphatase, al(1)-collagen, osteopontin and decorin were studied by northern blot analysis after 3 7 days' treatrnent with IL-6 in the concenttation range of 101,000 U/ml. Results: The mRNA levels for any of the osteoblastic proteins studied did not change significantly by IL-6 treatment up to the concentration of 1,000 U/ml. Conclusion: These results suggest that IL-6 does not have a significant role in differentiatian or activities of human bone rnarrow stromal (osteoprogenitor) cells (J Kor Soc Endocrinol ll:156 162, 1996).

8주간의 유산소성 체조활동을 통한 뇌병변 장애인의 체력 및 염증반응지표 변화

허금 ( Keum Heo ),김광준 ( Kwang Jun KIm ),김권일 ( Kwon Il Kim ),박동호 ( Dong Ho Park ),전태원 ( Tae Won Jun ),송욱 ( Wook Song ) 한국특수체육학회 2009 한국특수체육학회지 Vol.17 No.4

본 연구의 목적은 뇌병변 장애인을 대상으로 8주간의 유산소성 체조활동을 실시하여 신체조성, 체력 및 염증반응지표의 변화에 대하여 알아보는 것이다. 본 연구의 피험자는남·녀 뇌병변장애 중 대표적인 뇌졸중 장애인 17명을 대상으로 시작되었지만 9명이 중도포기하여 최종 8명이 참가하였다. 운동 프로그램 참여 전 사전 검사를 실시하였으며, 기본적 변인으로 신장, 체중, Body Mass Index(BMI), 안정시 심박수, 안정시 혈압을 측정하고, 체력 변인으로는 체간 굴곡과 신전, 견관절 굴곡과 신전의 유연성과 악력을 통한근력, 폐활량을 통한 폐기능을 측정하였다. 또한 혈액성분으로는 혈중지질, 그리고 심혈 관질환 위험인자인 염증반응지표로서 C-reactive protein(CRP), Interleukin-6(IL-6), Tumor Necrosis Factor-α(TNF-α)를 분석하였다. 8주 유산소성 체조활동 프로그램은 매회50분씩 주 2회 실시하였으며, 운동강도는 운동자각도(RPE) 수준 13으로 유지하였다. 뇌병변 장애인의 유산소성 체조활동 프로그램 참여 후 운동의 효과를 검증한 결과 전체 집단에서 안정시 수축기혈압과 이완기혈압이 유의하게 감소하였다(p<.01). 또한 체력 요인에서는 체간 굴곡과 신전(p<.05), 건측의 견관절 굴곡과 신전(p<.01), 환측의 견관절 굴곡(p<.05)이 유의하게 증가하였다. 혈액 성분의 분석 결과 혈중지질에는 유의한 변화가 나타나지 않았으며, 염증반응지표의 경우 IL-6가 유의하게 감소하였고(p<.05), 유의하지는 않으나 CRP도 감소하는 경향을 나타냈다(p<.088). 결론적으로, 지속적이고 규칙적인 유산소성 체조활동은 뇌병변 장애인의 안정시 심박수와 혈압 및 체력을 개선시키는 효과가 있을 뿐만 아니라 심혈관질환의 위험요소로 알려져 있는 염증반응지표를 개선하는 데에도 긍정적인 영향을 주는 것으로 나타났다. The purpose of this study was to analysis the effect of aerobic gymnastic exercise for eight weeks on physical fitness and inflammatory markers which are known as risk factors for cardiovascular diseases in hemiplegic disabled after cerebral stroke. For this purpose, stroke patients(n=8) participated in aerobic exercise training 2 days/week, 50 mins/day, for 8 weeks and maintained at 13 level of RPE. Body composition, resting heart rate and blood pressure were measured before physical fitness test. Trunk flexion/extension, shoulder flexion/extension, grip strength, pulmonary function were measured as physical fitness test. Blood sample of 15ml was drawn from antecubital veins for measuring inflammatory markers(c-reactive protein, interleukin-6, tumor necrosis factor-α). The result of this study is as follows: Resting blood pressure decreased significantly after 8-week aerobic exercise training in total stroke patients (p<.01). After completion of the aerobic exercise program, trunk extension/flexion(p<.05), shoulder extension/fexion(p<.01), were significantly improved in total stroke patients. There was no significant improvement on blood lipid profiles in total stroke patients. However, IL-6 was significantly improved in stroke patients after 8-week aerobic exercise(p<.05). In conclusion, These findings suggests that regular aerobic gymnastic exercise decreases resting heart rate and blood pressure, and improves physical fitness, inflammatory markers which are known as a risk factor of cardiovascular diseases in person with disability occurred due to hemiparetic stroke