위암에서 Helicobacter pylori cagA, vacA, iceA 유전자와 숙주 Interleukin-1β및 Interleukin-1 수용체 길항제 유전자 다형성

이성훈 ( Seong Hun Lee ),김태오 ( Tae Oh Kim ),이동현 ( Dong Hyun Lee ),박원일 ( Won Il Park ),김광하 ( Gwang Ha Kim ),허정 ( Jeong Heo ),강대환 ( Dae Hwan Kang ),송근암 ( Geun Am Song ),조몽 ( Mong Cho ) 대한내과학회 2006 대한내과학회지 Vol.71 No.1

Background: Both Helicobacter pylori (H. pylori) cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms play a role in determining the clinical consequences of H. pylori infection. This study aimed to investigate whether there might be any combinations of H. pylori cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms that are particularly associated with the occurrence of gastric carcinoma in Korean patients. Methods: This study population was comprised of 239 patients with H. pylori infection: 122 with gastric carcinoma and 117 with gastritis only. DNA was isolated from gastric biopsy sample and H. pylori cagA, vacA and iceA genotype were determined by PCR. IL-1B-511 polymorphisms were genotyped by PCR-RFLP and IL-1RN polymorphisms were analyzed with variable number of tandom repeat after PCR. Results: H. pylori cagA, vacA, and iceA genotype were not associated with an increased risk for gastric carcinoma. IL-1B-511*T carriers and IL-1RN*2 carriers did not show increased risk for gastric carcinoma. On combination of bacterial/host genotypes, cagA+/IL-1B-511*T carriers and cagA+/IL-1RN*2 carriers, vacA s1/IL-1B-511*T carriers, vacA s1/IL-1RN*2 carriers, vacA m1/IL-1B-511*T carriers, vacA m1/IL-1RN*2 carriers, iceA1/IL-1B-511*T carriers, iceA1/IL-1RN*2 carriers showed no increased risk of gastric carcinoma. Conclusions: Combined H. pylori cagA, vacA, iceA genotype and host IL-1B/IL-1RN polymorphisms shows no increased risk of gastric carcinoma. Therefore, it seems other endogenous or exogenous factors may play more important role in the development of gastric carcinoma in Korean.(Korean J Med 71:24-37, 2006)

The enhanced IL-l8 production by UVB irradiation requires ROI and AP-1 signaling in human keratinocyte cell line (HaCaT)

Cho, Daeho,Kang, Jae Seung,Park, Jong Hoon,Kim, Young-In,Hahm, Eunsil,Lee, Junechul,Yang, Yoolhee,Jeon, Junho,Song, HyunKeun,Park, Hyunjeong,Kim, Taesung,Pang, Saic,Kim, Chul-Woo,Hwang, Young Il,Lee, 전남대학교 약품개발연구소 2002 약품개발연구지 Vol.11 No.-

Based on our recent observation that enhanced IL-18 expression positively correlates with malignant skin tumors, such as SCC and melanoma, we examined the possible role of UVB, known to be associated with skin cancer development, in the enhancement of IL-18 production using primary human epidermal keratinocytes and human cell line HaCaT. After cells were exposed to UVB irradiation in vitro, IL-18 production was examined by Northern blot analysis and ELISA, and it was found that IL-18 production is enhanced by UVB irradiation in a dose- and time-dependent manner. In addition, we confirmed that it is functionally active form of IL-18 using the inhibitor of caspase-1. The effect of UVB irradiation was blocked by antioxidant, N-acetyl-ι-cysteine (NAC), which suggested the involvement of reactive oxygen intermediates (ROI) in the signal transduction of UVB irradiation-enhanced IL-18 synthesis. We also found that UVB irradiation increased AP-1 binding activity by using EMSA with AP-1-specific oligonucleotide. Furthermore, inhibitors of UVB-induced AP-1 activity, such as PD98059, blocked enhanced IL-18 production, indicating that AP-1 activation is required for UVB-induced IL-18 production. Taken together, our results suggest that UVB irradiation-enhanced IL-18 production is selectively mediated through the generation of ROI and the activation of AP-1.

Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</P>

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

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

Anti-inflammatory Effect of Gyulpidaehwangbakcho-tang (Jupidahuangpoxiao-tang) in the Collagen-induced Arthritis Mouse Model

Song, Young-Il,Oh, Min-Seok The Society of Korean Medicine 2011 대한한의학회지 Vol.32 No.6

Objectives: To investigate anti-inflammatory and anti-arthritic effects of Gyulpidaehwangbakcho-tang (GDBT) extract in a murine model of rheumatoid arthritis. Methods: The mice received $100{\mu}g$ of bovine type II collagen in Freund's complete adjuvant by intradermal injection at the base of the tail on day 0 and a booster injection on day 21. The mice were orally administered with GDBT (200 or 50mg/kg dissolved in distilled water) daily from day 1 to day 21 after arthritis incidence, and monitored for disease incidence and the severity of arthritis up to day 21. In order to evaluate the effect of GDBT on disease progression, we examined pro-inflammatory cytokines including IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II. Results: GDBT produced a significant and dose dependent inhibition of arthritis and inflammation during the entire duration of the study. This action was characterized by the decreased production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, and NOS-II in vivo. Conclusion: We believe that the anti-arthritic activity of GDBT is due to its modulatory effect on the expression of pro-inflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of GDBT in the treatment of RA and other inflammatory joint disorders.

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

송인숙,이상구,박정식,양원석,김순배,윤견일 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.5

Human peritoneal mesothelial cells may have a great potential to secrete chemokines, growth factors, adhesion molecules, and various cytokines stimulated with proinflammatory cytokines during peritoneal infection. In the course of peritonitis, rapid neutrophil cell influx and subsequent monocytic cell influx can be observed. It has been demonstrated that human peritoneal mesothelial cells secrete a C-X-C chemokine, IL-8, which contributes to the recruitment of neutrophil influx during peritoneal infection. However, the production and role of C-C chemokines have not been fully defined in human peritoneal mesothelial cells. This study was performed to evaluate the production of MCP-1 and RANTES and their influence on the chemotaxis of monocytes when human peritoneal mesothelial cells were stimulated with IL-1β. Mesothelial cells obtained by enzymatic digestion of pieces of human omentum and stimulated with a various doses and times of IL-1β. The expression of MCP-1 and RANTES mRNA was measured by Northern bloassay and the expression of their proteins was analyzed by ELISA. To evaluate their function, monocytes chemotaxis assay was performed using a 48-well chemotactic chamber. Cultured human peritoneal mesothelial cells appeared to be polygonal at confluence using phase contrast microscope. Indirect immunofluorescent staining demonstrated that the mesothelial cells reacted positively with anti-cytokeratin antibody and anti-vimentin antibody. The expression of MCP-1 and RANTES mRNA increased in response to IL-1β in time and dose dependent manner. The protein levels of MCP-1 and RANTES with stimulation of 1.0ng/mL of IL-1β for 24 hours were higher than those without(30.0±2.22 vs 3.55±0.74ng/105cells and 1.53±0.41 vs 0.11±0.02ng/105cells respectively, p$lt;0.05, n=6). Chemotaxis assay showed that the supernatants from human peritoneal mesothelial cells with stimulation of IL-1β for 24 hours had significantly higher chemotaxis of monocytes than those without(71±3.4% vs 50±2.9%, p$lt;0.05, n=6). Coincubation of sup with stimulation and antibodies to MCP-1 or RANTES(20μL/mL, lOμL/mL, respectively) resulted in a significant inhibition of chemotaxis of monocytes by 33% and 12%(47±3.1% and 62±3.0% respectively, p$lt;0.05, n=6). Human peritoneal mesothelial cells are capable of the expression of MCP-1 and RANTES mRNA and the production of their proteins in response to IL-1β. Functionally, mesothelial cells derived Mand RANTES may contribute to the recruitment of monocytes and amplify the inflammatory process. Thus, human peritoneal mesothelial cells play an important role during peritoneal infection.

Anti-inflammatory Effect of Gyulpidaehwangbakcho-tang(Jupidahuangpoxiao-tang) in the Collagen-induced Arthritis Mouse Model

Young-Il Song,Min-Seok Oh 대한한의학회 2011 대한한의학회지 Vol.32 No.6

Optimizing DC Vaccination by Combination With Oncolytic Adenovirus Coexpressing IL-12 and GM-CSF

Zhang, Song-Nan,Choi, Il-Kyu,Huang, Jing-Hua,Yoo, Ji-Young,Choi, Kyung-Ju,Yun, Chae-Ok Nature Publishing Group 2011 MOLECULAR THERAPY Vol.19 No.8

<P>Dendritic cell (DC)-based vaccination is a promising strategy for cancer immunotherapy. However, clinical trials have indicated that immunosuppressive microenvironments induced by tumors profoundly suppress antitumor immunity and inhibit vaccine efficacy, resulting in insufficient reduction of tumor burdens. To overcome these obstacles and enhance the efficiency of DC vaccination, we generated interleukin (IL)-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-coexpressing oncolytic adenovirus (Ad-ΔB7/IL12/GMCSF) as suitable therapeutic adjuvant to eliminate immune suppression and promote DC function. By treating tumors with Ad-ΔB7/IL12/GMCSF prior to DC vaccination, DCs elicited greater antitumor effects than in response to either treatment alone. DC migration to draining lymph nodes (DLNs) dramatically increased in mice treated with the combination therapy. This result was associated with upregulation of CC-chemokine ligand 21 (CCL21<SUP>+</SUP>) lymphatics in tumors treated with Ad-ΔB7/IL12/GMCSF. Moreover, the proportion of CD4<SUP>+</SUP>CD25<SUP>+</SUP> T-cells and vascular endothelial growth factor (VEGF) expression was decreased in mice treated with the combination therapy. Furthermore, combination therapy using immature DCs also showed effective antitumor effects when combined with Ad-ΔB7/IL12/GMCSF. The combination therapy had a remarkable therapeutic efficacy on large tumors. Taken together, oncolytic adenovirus coexpressing IL-12 and GM-CSF in combination with DC vaccination has synergistic antitumor effects and can act as a potent adjuvant for promoting and optimizing DC vaccination.</P>

방풍의 항염 효과 기전

노성일 ( Sung Il Noh ),김상돈 ( Sang Don Kim ),박성철 ( Sung Cheul Park ),서병윤 ( Byung Yun Seo ),염승룡 ( Seung Ryong Yeom ),권영달 ( Young Dal Kwon ),신병철 ( Byung Cheul Shin ),송용선 ( Yung Sun Song ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.2

목적 : 방풍은 임상적으로 관절염을 포함한 다양한 염증성 질환 치료제로 사용되어 왔다. 본 연구에서는 인간 비만세포를 이용하여 세포 독성에 영향을 주지 않는 농도에서 방풍의 항염 효과 및 그 기전을 검토했다. 방법 : 인간의 HMC-1세포를 IMDM에서 페니실린, 스트렙토마이신, 모노티오글리세린를 첨가하여 배양하고 방풍추출액을 투여하였다. 그 다음 MTT, ELISA, RT-PCR, 세포내 칼슘측정, 핵단백분석을 이용하여 TNF-α, IL-6, IL-8 각각의 형성과 mRNA발현, 세포내 칼슘 수준, NF-κB 발현에 대한 방풍추출액의 반응을 측정하고 통계처리 하였다. 결과 : 방풍은 PMA와 calcium ionophore A23187로 활성화된 비만세포에서 세포내 칼슘 수준과 NF-κB, TNF-α와 IL-6의 발현을 억제 시켰고 RT-PCR을 이용한 mRNA 발현에서 TNF-α와 IL-6의 발현을 억제하였다. 결론 : 방풍은 비만세포내 칼슘 수준 및 NF-κB의 활성을 억제하고 염증성 세포 활성 물질인 TNF-α와 IL-6의 분비도 억제하여 항염 효과를 나타냄을 암시하고 있다.

Therapeutic and Tumor-specific Immunity Induced by Combination of Dendritic Cells and Oncolytic Adenovirus Expressing IL-12 and 4-1BBL

Huang, Jing-Hua,Zhang, Song-Nan,Choi, Kyung-Ju,Choi, Il-Kyu,Kim, Joo-Hang,Lee, Mingul,Kim, Hoguen,Yun, Chae-Ok Nature Publishing Group 2010 MOLECULAR THERAPY Vol.18 No.2

<P>Recently, gene-based cytokine treatment has been actively pursued as a new promising approach in treating cancer. In an effort to augment the efficiency of antitumor effect by cytokine-mediated immunotherapy, we selected both interleukin (IL)-12 and 4-1BB ligand (4-1BBL) as suitable cytokines to fully activate the type-1 immune response. Coexpression of IL-12 and 4-1BBL mediated by oncolytic adenovirus (Ad) greatly enhanced the antitumor effect. Further, synergistic enhancement in interferon (IFN)-γ levels were seen in mice treated with oncolytic Ad expressing both IL-12 and 4-1BBL. Next, to improve the overall antitumor immune response, we coadministered IL-12- and 4-1BBL-coexpressing oncolytic Ad with dendritic cells (DCs). Combination treatment of IL-12- and 4-1BBL-coexpressing oncolytic Ad and DCs elicited greater antitumor and antimetastatic effects than either treatment alone. Moreover, enhanced type-1 antitumor immune response and higher migratory abilities of DCs in tumors were also observed in the combination arms. The nature of the enhanced antitumor immune response seems to be mediated through the enhanced cytolytic activity of cytotoxic T lymphocytes (CTLs) and IFN-γ-releasing immune cells. Taken together, these data highlight the potential therapeutic benefit of combining IL-12- and 4-1BBL-coexpressing oncolytic Ad with DCs and warrants further evaluation in the clinic.</P>