Interleukin-1B(1L-1B) polymorphisms and gastric mucosal levels of IL-Iβ cytokine in Korean patients with gastric cancer

Chang, Young-Woon,Jang, Jae-Young,Kim, Nam-Hoon,Lee, Jae Won,Lee, Hyo Jung,Jung, Woon Won,Dong, Seok-Ho,Kim, Hyo-Jong,Kim, Byung-Ho,Lee, Joung-Il,Rin Chang KYUNG HEE UNIVERSITY MEDICAL CENTER 2006 고황의학상 수상논문집 Vol.21-22 No.-

Interleukin-1B and IL-1 receptor antagonist gene polymorphisms are associated with an increased risk of gastric cancer (GC) in Caucasian populations. However, recent studies could not find any association between IL-1B-511T polymorphism and the risk of GC in Asians. We tested for an association between IL-1 loci polymorphisms with increased gastric mucosal levels of IL-1β and an increased risk of developing GC in a Korean population. Polymorphisms of IL-1A-889, IL-1B-31, IL-1B-511 and IL-1RN were genotyped in 434 controls and 234 patients with GC. Mucosal IL-1β cytokine was measured using an ELISA. The frequencies of IL-1A, IL-1B-511, IL-1B-31 and IL-1RN were not statistically different between controls and all patients with GC. After subclassification of GC, only patients with intestinal-type GC showed a higher frequency of IL-1B-31T homozygotes (OR = 2.2; 95% CI = 1.1-4.3) compared with controls. Risk was also significantly increased in these patients for IL-1B-31T homozygotes compared with patients with diffuse-type GC (OR = 3.4; 95% CI = 1.5-7.7). As in Caucasian populations, linkage disequilibrium between IL-1B-31 and IL-1B-511 was nearly complete, but the pattern of haplotype related to the risk of GC (IL-1B-31T/IL-1B-511C) was opposite (IL-1B-511T/IL-1B-31C). Mucosal IL-1β levels in H. pylori-infected GC patients were higher in patients homozygous for IL-1B-31T compared with IL-1B-31C/T and IL-1B-31C/C. Thus, the combined effects of H. pylori infection and IL-1B-31T/IL-1B-511C polymorphisms with enhanced mucosal IL-1β production contributed to the development of intestinal-type GC in this Korean population.

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>

금은화, 연교, 포공영 혼합물의 항염증 작용에 관한 연구

최강민 ( Kang Min Choi ),전주현 ( Ju Hyun Jeon ),김은석 ( Eun Seok Kim ),성기정 ( Ki Jung Sung ),김영일 ( Young Il Kim ) 대전대학교 한의학연구소 2021 혜화의학회지 Vol.30 No.1

Objective : The purpose of this study is to investigate the inflammatory-control effects of Cheonghyeol-antidote complex(Lonicera japonica Thunberg, Forsythia viridissima Lindley, and Taraxacum platycarpum H. Dahlstedt complex, CHA) in LPS-induced RAW264.7 cell and mouse inflammation models. Method : For in vitro and in vivo experiment, Indicators such as cell viability, mRNA expression level(iNOS, IL-6, IL-1β, COX-2, TNF-a), Inflammatory factor production(NO, IL-6, IL-1β, TNF-a), and protein phosphorylation level(ERK, JNK, p38) were analyzed. For in vivo experiment, Indicators such as mRNA expression level(iNOS, IL-6, IL-1β, COX-2, TNF-a), Inflammatory factor production(IL-6, IL-1β, TNF-a), protein phosphorylation level(ERK, JNK, p38) and immune cell(white blood cell, lymphocyte) were analyzed. Results : 1. In vitro experiment In cell viability of CHA, CHA showed cell viability below 90% at concentrations of 400 μg / ml or more. In mRNA expression level, IL-6 and IL-1β showed a significant decrease at all concentrations except 25 μg / ml concentration, and iNOS, COX-2, and TNF-a showed a significant decrease at all concentrations of CHA compared to the control group. In inflammatory factor production, NO and TNF-a showed a significant decrease at all concentrations except 25 μg / ml concentration of CHA, and IL-1β showed a significant decrease at 100, 200 μg / ml concentration of CHA compared to the control group. IL-6 showed a significant decrease at all concentration of CHA compared to the control group. In protein phosphorylation level, ERK and p38 showed a significant decrease at all concentrations except 25 μg / ml concentration of CHA and JNK showed a significant decrease at all concentrations of CHA compared to control group. 2. In vivo experiment In mRNA expression level, iNOS, COX-2 and TNF-a showed a significant decrease in all administration groups of CHA compared to the control group. In Inflammatory factor production, IL-6, IL-1β and TNF-a showed a significant decrease in all the administration groups of CHA. In protein phosphorylation level, ERK, JNK, and p38 showed a significant decrease in all the administration groups of CHA. In the immune cells, leukocytes and lymphocytes showed a significant decrease in all the administration groups of CHA. Conclusions : This study shows that CHA has antioxidant and inflammatory-control effects on LPS-induced RAW264.7 cells. It is hoped that further research will be conducted on the individual mechanisms of Lonicera japonica Thunberg, Forsythia viridissima Lindley, and Taraxacum platycarpum H. Dahlstedt.

Early Phase of UVB - induced GM - CSF Upregulation in Epithelial Cell Line is not Totally Dependent on IL - 1α

Park, Kyoung Chan,Kim, Kyu Han,Ahn, Jong Seong,Chung, Jin Ho,Youn, Jai Il,Whang, Ji Hwan,Youn, Sang Woong,Kim, Young Gull,Koh, Woo Seok,Jung, Hyun Chae 대한피부과학회 1997 Annals of Dermatology Vol.9 No.4

Backgrounds : It was demonstrated that ultraviolet(UV) B light induces the release of IL-la in cultured human epithelial cell line and augmentation of GM-CSF production by UVB is reported to be mediated by IL-1α in the murine keratinocyte cell line Pam 212. Objective : The purpose of this study was to evaluate the effects of UVB on kinetic profile of IL-1 and GM-CSF mRNA expression and to see whether synthesis of GM-CSF by UVB can be completely inhibited by blocking IL-1α mediated pathway. Method : We used a competitive RT-PCR for measuring cytokine gene expression in epithelial cell line after UV radiation. Results : The IL-1α mRNA increased as early as 1h after UV irradiation, and then decreased at 3h after the irradiation. Thereafter, the response of IL-1α mRNA was upregulated with a second peak at 6h after the UV irradiation. However, mRNA for GM-CSF increased at 1h after UV light exposure and anti-IL-1α antibodies could only partially inhibit UV-augmented GMCSF production. Conclusion : UVB induced GM-CSF production seemed to be mainly mediated by UVB induced IL-1α but these results suggest that UVB may also induce GM-CSF production through an IL-1α independent pathway.

S-562 : MicroRNA-155 as a proinflammatory regulator in acute gouty arthritis

( Jung Ho Choi ),( Hye Mi Jin ),( Moon Ju Kim ),( Young Nan Cho ),( Kwang Il Nam ),( Seung Jung Kee ),( Jang Bae Moon ),( Dong Jin Park ),( Yong Wook Park ),( Shin Seok Lee ),( Tae Jong Ki ) 대한내과학회 2013 대한내과학회 추계학술대회 Vol.2013 No.1

Introduction: MicroRNA-155 (miR-155) is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. Since, the functional role of miR-155 in gouty arthritis has not been defined. The aim of this study was to examine the role of miR-155 in pathogenesis of gouty arthritis. Materials and methods: Samples from fourteen patients with gouty arthritis and ten healthy controls were obtained. Monosodium urate (MSU) crystals were prepared by recrystallization from uric acid. Total RNA was isolated using the miRNeasy kit (Qiagen). The miScript Reverse Transcription Kit (Qiagen) was used for cDNA preparation. MiScript primer assay (Qiagen) were used for semiquantitative determination of the expression of human miR-155. Human TNF-α and IL-1β in supernatants were measured by Luminex (Millipore, USA) according to the instructions of the manufacturer. Gout peritonitis mice (Male C57BL/6J) model used to analyze expressions of miR-155, Src homology 2-containing inositol phosphatase-1 (SHIP-1), and inflammatory cytokines. Results: The samples from gout patients proved to be highly enriched in miR-155, with levels of expression being 4-fold higher than those found in peripheral blood mononuclear cells (PBMC) from healthy controls and gout (p<0.05). miR-155 was found to be strongly induced by stimulation of MSU crystals after 24 hours and their expressions gradually decreased. Stimulating with MSU crystals for the indicated times, and the level of SHIP-1 was found to be gradually decreased in according to over-expression of miR-155. miR-155 promoted MSU-induced proinflammatory cytokine production. Commensurate with our observations in human synovial monocytes, miR-155 expression was elevated in gout mice model. SHIP-1 protein levels were markedly reduced in cells by MSU stimulated, compared to the control. MSU crystal induced peritonitis mice significantly increased the production of inflammatory cytokines, such as TNF-α and IL-1β. Conclusion: Overexpression of miR-155 in synovial fluid mononuclear cells (SFMC) led to down-regulation of SHIP-1 and an increase in the production of proinflammatory cytokines.

Anti-allergic effects of a nonameric peptide isolated from the intestine gastrointestinal digests of abalone (Haliotis discus hannai) in activated HMC-1 human mast cells

KO, SEOK-CHUN,LEE, DAE-SUNG,PARK, WON SUN,YOO, JONG SU,YIM, MI-JIN,QIAN, ZHONG-JI,LEE, CHANG-MIN,OH, JUNGHWAN,JUNG, WON-KYO,CHOI, IL-WHAN Spandidos Publications 2016 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.37 No.1

<P>The aim of the present study was to examine whether the intestine gastrointestinal (GI) digests of abalone [Halioti s discus hannai (H. discus hannai)] modulate inflammatory responses and to elucidate the mechanisms involved. The GI digests of the abalone intestines were fractionated into fractions I (>10 kDa), 11 (5-10 kDa) and III (<5 kDa). Of the abalone intestine GI digests (AIGIDs), fraction III inhibited the passive cutaneous anaphylaxis (PCA) reaction in mice. Subsequently, a bioactive peptide [abalone intestine GI digest peptide (AIGIDP)] isolated from fraction III was determined to be 1175.2 Da, and the amino acid sequence was found to be PFNQGTFAS. We noted that the purified nonameric peptide (AIGIDP) attenuated the phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-induced histamine release and the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6 in human mast cells (HMC-1 cells). In addition, we also noted that AIGIDP inhibited the PMACI-induced activation of nuclear factor-kappa B (NF-kappa B) by suppressing I kappa B alpha phosphorylation and that it suppressed the production of cytokines by decreasing the phosphorylation of JNK. The findings of our study indicate that AIGIDP exerts a modulatory, anti-allergic effect on mast cell-mediated inflammatory diseases.</P>

The Free Radical Scavenger NecroX-7 Attenuates Acute Graft-versus-Host Disease via Reciprocal Regulation of Th1/Regulatory T Cells and Inhibition of HMGB1 Release

Im, Keon-Il,Kim, Nayoun,Lim, Jung-Yeon,Nam, Young-Sun,Lee, Eun-Sol,Kim, Eun-Jung,Kim, Hyoung Jin,Kim, Soon Ha,Cho, Seok-Goo The American Association of Immunologists, Inc. 2015 JOURNAL OF IMMUNOLOGY Vol.194 No.11

<P>Graft-versus-host disease (GVHD) is a major complication associated with allogeneic hematopoietic stem cell transplantation. Despite the prominent role of the adaptive immune system, the importance of controlling the innate immune system in the pathogenesis of GVHD has recently been rediscovered. High-mobility group box 1 (HMGB1) is a crucial damage-associated molecular pattern signal that functions as a potent innate immune mediator in GVHD. In the present study, we investigated treatment of experimental GVHD through HMGB1 blockade using the compound cyclopentylamino carboxymethylthiazolylindole (NecroX)-7. Treated animals significantly attenuated GVHD-related mortality and inhibited severe tissue damage. These protective effects correlated with the decrease in HMGB1 expression and lower levels of reactive oxidative stress. Additionally, NecroX-7 inhibited the HMGB1-induced release of TNF and IL-6, as well as the expression of TLR-4 and receptor for advanced glycation end products. We also observed increased regulatory T cell numbers, which may be associated with regulation of differentiation signals independent of HMGB1. Taken together, these data indicate that NecroX-7 protects mice against lethal GVHD by reciprocal regulation of regulatory T/Th1 cells, attenuating systemic HMGB1 accumulation and inhibiting HMGB1-mediated inflammatory response. Our results indicate the possibility of a new use for a clinical drug that is effective for the treatment of GVHD.</P>

Regulation of UVB-Induced IL-8 and MCP-1 Production in Skin Keratinocytes by Increasing Vitamin C Uptake via the Redistribution of SVCT-1 from the Cytosol to the Membrane

Kang, Jae Seung,Kim, Ha Na,Jung, Da Jung,Kim, Jee Eun,Mun, Ga Hee,Kim, Yeong Seok,Cho, Daeho,Shin, Dong Hoon,Hwang, Young-Il,Lee, Wang Jae Williams & Wilkins 2007 The Journal of investigative dermatology Vol.127 No.3

It is well known that UVB (290–320 nm) induces inflammation in skin by the transcription and release of cytokines and chemokines from skin keratinocytes. In addition, it is considered that intracellular reactive oxygen species (ROS) plays an important role in UVB-induced inflammatory response in the skin. Therefore, we investigated the effect of vitamin C, a potent antioxidant, on the regulation of UVB-induced skin inflammation via the modulation of chemokines production. Vitamin C uptake into keratinocytes is increased by UVB irradiation in a time- and dose-dependent manner through the translocation of sodium-dependent vitamin C transporter-1 (SVCT-1), a vitamin C-specific transporter, from the cytosol to the membrane. To evaluate the effect of vitamin C on the chemokine mRNA expression, we performed RNase protection assay. As a result, there was a remarkable change in chemokine mRNA expression, especially IL-8 and monocyte chemoattractant protein (MCP)-1 expression. In addition, increased IL-8 and MCP-1 mRNA expressions were suppressed by vitamin C treatment. We also confirmed the results of protein levels measured by ELISA. Taken together, vitamin C uptake is increased in UVB-irradiated keratinocytes through the translocation of SVCT-1 and regulates inflammatory response in the skin via the downregulation of IL-8 and MCP-1 production.Journal of Investigative Dermatology (2007) 127, 698–706. doi:10.1038/sj.jid.5700572; published online 28 September 2006

복막 중피 세포에서 IL-1β 자극에 의한 MCP-1과 RANTES의 생성

송인숙,양원석,이상구,윤견일,박정식,김순배 대한신장학회 2000 대한신장학회잡지 Vol.19 No.5

MicroRNA-155 as a proinflammatory regulator via SHIP-1 down-regulation in acute gouty arthritis

Jin, Hye Mi,Kim, Tae-Jong,Choi, Jung-Ho,Kim, Moon-Ju,Cho, Young-Nan,Nam, Kwang-Il,Kee, Seung-Jung,Moon, Jang Bae,Choi, Seok-Yong,Park, Dong-Jin,Lee, Shin-Seok,Park, Yong-Wook BioMed Central 2014 ARTHRITIS RESEARCH AND THERAPY Vol.16 No.2

<P><B>Introduction</B></P><P>Gout is characterized by episodes of intense joint inflammation in response to intra-articular monosodium urate monohydrate (MSU) crystals. miR-155 is crucial for the proinflammatory activation of human myeloid cells and antigen-driven inflammatory arthritis. The functional role of miR-155 in acute gouty arthritis has not been defined. Therefore, the aim of this study was to examine the role of miR-155 in pathogenesis of acute gouty arthritis.</P><P><B>Methods</B></P><P>Samples from 14 patients with acute gouty arthritis and 10 healthy controls (HCs) were obtained. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were cultured <I>in vitro</I> with MSU crystals, and gene expression (human miR-155 and SHIP-1) were assessed by real-time PCR. THP-1 cells were stimulated by MSU crystals and/or miR-155 transfection and then subjected to Western blot analysis. Levels of human tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-1β in cell culture supernatants were measured by Luminex. Immunohistochemistry was performed on formalin-fixed gout tissues with anti–SHIP-1 antibody. A C57BL/6 J male mouse model of gout was used to analyze the expressions of miR-155, SHIP-1, and inflammatory cytokines.</P><P><B>Results</B></P><P>The samples from gouty arthritis were highly enriched in miR-155, with levels of expression being higher than those found in PBMC from HC. Treatment of the cells with MSU crystals strongly induced miR-155. In addition, overexpression of miR-155 in the cells decreased levels of SHIP-1 and promoted production of MSU-induced proinflammatory cytokines, such as TNF-α and IL-1β. Consistent with <I>in vitro</I> observations, miR-155 expression was elevated in the mouse model of gout. The production of inflammatory cytokines was markedly increased in MSU crystal induced peritonitis mice.</P><P><B>Conclusions</B></P><P>Overexpression of miR-155 in the gouty SFMC leads to suppress SHIP-1 levels and enhance proinflammatory cytokines.</P>