The Correlation of Serum IL-12B Expression With Disease Activity in Patients With Inflammatory Bowel Disease

Lee, Hye Won,Chung, Sook Hee,Moon, Chang Mo,Che, Xiumei,Kim, Seung Won,Park, Soo Jung,Hong, Sung Pil,Kim, Tae Il,Kim, Won Ho,Cheon, Jae Hee Williams & Wilkins Co 2016 Medicine Vol.95 No.23

<▼1><P>Supplemental Digital Content is available in the text</P></▼1><▼2><P><B>Abstract</B></P><P>Genetic variants in <I>IL12B</I>, encoding the p40 subunit common in interleukin-12 (IL-12) and interleukin-23, were identified as the susceptibility loci for inflammatory bowel disease (IBD). This study aimed to identify the correlation of serum IL-12B expression with disease activity in patients with IBD and evaluate the possibility of IL-12B as a biomarker for assessing inflammatory status in IBD.</P><P>A total of 102 patients with IBD, including 38, 32, and 32 patients with Crohn's disease (CD), ulcerative colitis (UC), and intestinal Behçet's disease (intestinal BD), respectively, were included. The clinical and laboratory data from the patients were collected at the time of serum IL-12B measurement. Serum IL-12B levels were measured using an enzyme-linked immunosorbent assay.</P><P>The median IL-12B levels in patients with CD, UC, and intestinal BD were significantly higher than those in controls (1.87, 2.74, and 2.73 pg/mL, respectively, vs. 1.42 pg/mL, all <I>P</I> <0.05). IL-12B concentrations were associated with disease activity in patients with UC and intestinal BD but not in those with CD. IL-12B levels were increased with increasing disease activity in patients with UC (<I>P</I> <0.001). Likewise, patients with active intestinal BD had higher IL-12B levels than those without active disease (<I>P</I> = 0.008). IL-12B levels were correlated with the endoscopic disease activity of UC (<I>P</I> = 0.002) and intestinal BD (<I>P</I> = 0.001) but not that of CD.</P><P>Serum IL-12B levels were significantly correlated with clinical and endoscopic disease activity in patients with UC and intestinal BD, suggesting its potential use as a biomarker for assessing disease activity in these patients.</P></▼2>

담배 니코틴에 의한 사람 태아 성상세포에서 종양괴사인자(TNF-α)의 발현 억제작용

손일홍,이성익,양현덕,한선정,석승한,이재규,김재현,박주영,문형인,이성수,Son, Il-Hong,Lee, Sung-Ik,Yang, Hyun-Duk,Han, Sun-Jung,Suk, Seung-Han,Lee, Jai-Kyoo,Kim, Jae-Hyun,Park, Joo-Young,Moon, Hyung-In,Lee, Sung-Soo 대한화학회 2007 대한화학회지 Vol.51 No.3

니코틴은 사람 대식세포에서 interleukin 2 (IL-2)와 종양괴사인자 (tumor necrosis factor-alpha; TNF-α) 가 생성되는 것을 억제하는데, 이러한 억제작용은 cytokine 유전자 발현 중 전사단계에서 전사인자의 활성을 억제함으로써 일어난다. 이러한 니코틴의 면역반응 억제작용은 아프타성궤양 및 궤양성대장염, 알레르기성폐 포염, 건초열 등에서도 보고되고 있다. 만일 중추신경계에서도 위와 같은 니코틴의 면역억제 작용이 일어난 다면 다발성경화증과 같은 면역반응 매개질환의 치료에 새로운 전기가 마련될 수 있을 것이다. 본 연구에서 는 중추신경계의 여러 면역반응 매개질환의 병태생리에 대한 이해를 넓히고자, 이미 알려진 니코틴의 cytokine 생성억제가 사람 중추신경계의 성상세포에서도 일어남을 확인하고 그 억제기전을 밝히고자 하였다. 이를 위 하여 사람 태아 성상세포에 다양한 농도의 니코틴과 IL-1β를 처리한 다음 TNF-α mRNA의 발현 정도와 NF- κB의 활성을 비교, 분석하여 다음과 같은 결과를 얻었다. 1. 사람 태아 성상세포를 0.1-20 μg/ml의 니코틴으로 처리해 본 결과 10 μg/ml 이상의 농도에서 세포독성능이 나타나기 시작하였다. 2. 사람 태아 성상세포에 IL- 1β를 처리하면 2시간만에 TNF-α mRNA가 최대로 발현되었으며 그 이후로는 점진적으로 감소하였다. 3. 사 람 태아 성상세포를 1 및 0.1 μg/ml의 니코틴으로 전처리한 후 IL-1β로 자극한 군에서는 IL-1β 단독 처리군에 비해 TNF-α mRNA의 발현이 감소하는 양상을 보였다. 1 μg/ml의 니코틴을 처리한 경우에는 8시간 이후부터 TNF-α mRNA의 발현이 현저하게 감소하여 12시간에 최대로 감소하였다. 또한 0.1 μg/ml의 니코틴을 처리한 군에서는 24시간에 가장 현저하게 감소하였다. 4. 성상세포에 IL-1β로 처리한 군에서는 강력한 NF-κB의 활성 을 확인할 수 있었으며, 니코틴을 전처리하고 IL-1β 자극한 군에서는 NF-B의 활성이 감소하였다. 결론적으로 일정농도 이상의 니코틴은 세포독성효과를 나타내나 적정한 농도와 시간 경과후 니코틴은 사람 태아 성상세포에서 IL-1β에 의해 유도되는 TNF-α의 발현 감소를 유도하며, 이는 NF-κB의 활성을 감소시킴으로써 나타난다고 생각된다. The Tumor necrosis factor-α, (TNF-α), is involved in the pathogenesis of multiple sclerosis and contributes to the degeneration of oligodendrocytes as well as neurons. Nicotine has been found to have immunosuppressive and inflammation-suppressing effects. Astrocytes, the major glial cells in the CNS, are capable of producing TNF-α at both the mRNA and protein levels in response to interleukin-1 (IL-1) or TNF-α. Nicotine has been shown to influence glial cell functions. To order to explore the role of astrocytes in the production of TNF-α, astrocytes were pretreated with nicotine and are stimulated with IL-1β to determine their effects on TNF-α production. The results are as follows. Cytotoxic effects of nicotine on human fetal astrocytes were noted above 10 μg/ml of nicotine. The effect of IL-1β on TNF-α mRNA expression in primary cultured human fetal astrocytes was maximal at 2 h after IL- 1β(100 pg/ml) treatment. Human fetal astrocytes were pretreated with 0.1, 1, and 10 μg/ml of nicotine and then stimulated with IL-1β (100 pg/ml) for 2 h. The inhibitory effect of nicotine on expressions of TNF-α mRNA in human fetal astrocytes with pretreated 0.1 μg/ml of nicotine is first noted at 8 hr, and the inhibitory effect is maximal at 12 h. The inhibitory effect at 1 μg/ml of nicotine is inhibited maximal at 24 h. Nicotine at 0.1, 1 and 10 μg/ml concentrations significantly inhibits IL-1β-induced NF-κB activation. Collectively, this study indicates that nicotine might inhibit the expression of TNF-α in activated human fetal astrocytes.

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.

Association between chronic hepatitis B virus infection and interleukin-10, tumor necrosis factor-α gene promoter polymorphisms

Cheong, Jae Youn,Cho, Sung Won,Hwang, Il Lan,Yoon, Seung Kew,Lee, June Hyuk,Park, Choon Sik,Lee, Jong Eun,Hahm, Ki Baik,Kim, Jin Hong Blackwell Publishing Asia 2006 Journal of gastroenterology and hepatology Vol.21 No.7

<P>Abstract</P><P>Background: </P><P>The reasons for the viral persistence of hepatitis B virus infection (HBV) are unknown, but are probably related to host immune factors. Cytokines play a significant role in immune defense. The present study was undertaken to investigate the association between HBV infection and polymorphisms of tumor necrosis factor (TNF)-α and interleukin(IL)-10 gene promoter.</P><P>Methods: </P><P>A total of 412 Korean patients with HBV infection (72 inactive carriers, 261 witih chronic hepatitis, 79 with liver cirrhosis) and 204 healthy individuals who recovered from HBV infection, were studied. The polymorphisms in IL-10 gene promoter (−1082, −819, −592), and TNF-α gene promoter (−308, −238) were assessed by single base primer extension assay.</P><P>Results: </P><P>The frequency of C/C genotype at position −592 of IL-10 gene promoter was higher in the HBV clearance group than that in the persistence group in univariate analysis (12.7% vs 7.5%, <I>P</I> = 0.036). The IL-10 gene promoter −592 C/C genotype was related to clearance of HBV infection in logistic regression analysis after adjusting for age and sex (<I>P</I> = 0.003). Genotype frequencies of TNF-α gene promoter at position −308 and −238 were not different between the clearance and the persistence group in univariate analysis, but in multivariate analysis after adjusting for age and sex, −308G/−238G homozygotes were associated with HBV persistence (<I>P</I> = 0.005). Genotype distributions of both gene promoters in inactive carriers were similar to those in patients with chronic progressive liver disease.</P><P>Conclusions: </P><P>The carriers of the −592A allele in the IL-10 promoter and −308G/−238G haplotype homozygotes in the TNF-α promoter region have higher risk of persistent HBV infection.</P>

IRAK4 as a Molecular Target in the Amelioration of Innate Immunity–Related Endotoxic Shock and Acute Liver Injury by Chlorogenic Acid

Park, Sun Hong,Baek, Seung-Il,Yun, Jieun,Lee, Seungmin,Yoon, Da Young,Jung, Jae-Kyung,Jung, Sang-Hun,Hwang, Bang Yeon,Hong, Jin Tae,Han, Sang-Bae,Kim, Youngsoo American Association of Immunologists 2015 Journal of Immunology Vol. No.

<P>Mice lacking the IL-1R-associated kinase 4 (IRAK4) are completely resistant to LPS-induced endotoxic disorder or the TLR9 agonist CpG DNA plus D-galactosamine-induced acute liver injury (ALI), whereas wild-type strains succumb. However, translational drugs against sepsis or ALI remain elusive. Lonicerae flos extract is undergoing the clinical trial phase I in LPS-injected healthy human volunteers for sepsis treatment. In the current study, chlorogenic acid (CGA), a major anti-inflammatory constituent of lonicerae flos extract, rescued endotoxic mortality of LPS-intoxicated C57BL/6 mice, as well as ameliorated ALI of LPS/D-galactosamine-challenged C57BL/6 mice. As a mechanism, CGA inhibited various TLR agonist-, IL-1 alpha-, or high-mobility group box-1-stimulated autophosphorylation (activation) of IRAK4 in peritoneal macrophages from C57BL/6 or C3H/HeJ mice via directly affecting the kinase activity of IRAK4, a proximal signal transducer in the MyD88-mediated innate immunity that enhances transcriptional activity of NF-kappa B or AP-1. CGA consequently attenuated protein or mRNA levels of NF-kappa B/AP-1 target genes encoding TNF-alpha, IL-1 alpha, IL-6, and high-mobility group box-1 in vivo under endotoxemia or ALI. Finally, this study suggests IRAK4 as a molecular target of CGA in the treatment of innate immunity-related shock and organ dysfunction following insult of various TLR pathogens from bacteria and viruses.</P>

고욤잎, 감잎 및 뽕잎 복합추출물의 항아토피 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),신재영(Jae Young Shin),방숭주(Chong Zhou Fang),체 데니스 창(Chong Zhou Fang),장선일(Seon Il Jang) 한국식품영양과학회 2016 한국식품영양과학회지 Vol.45 No.4

본 연구는 고욤잎, 감잎 및 뽕잎을 단독으로 사용하기보다 혼합하여 사용할 경우 고욤잎, 감잎 및 뽕잎 복합추출물이 아토피 피부염(AD) 증상을 억제하는지 효과를 밝히고, 항염효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 건조 상태, 스케일링, 미란, 찰과상 및 홍반 같은 아토피 피부염 증상이 AD 모델에서 증가하였지만, 고욤잎, 감잎 및 뽕잎 각각의 추출물과 복합추출물을 투여하였을 경우 완화되는 것을 확인할 수 있었으며, 복합추출물이 고욤잎, 감잎 및 뽕잎 각각의 추출물보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증세포 및 비만세포의 침윤은 AD 모델에서 크게 증가하였지만, 고욤잎, 감잎 및 뽕잎 단독추출물과 복합추출물을 투여하였을 경우 감소하는 것을 확인할 수 있었으며, 복합추출물이 단독추출물보다 더 뛰어난 효과를 나타내었다. 혈청중의 IgE와 IL-4의 수치를 측정한 결과 AD 모델에서 많이 증가하였으나, 고욤잎, 감잎 및 뽕잎 단독추출물과 복합추출물을 투여하였을 경우 감소하는 것을 확인할 수 있었으며, 복합추출물이 단독추출물보다 더 뛰어나게 억제하는 효과를 나타내었다. HMC-1 세포에 복합추출물을 처리하였을 경우 염증성 사이토카인인 TNF-α와 IL-6의 생성량이 유의적으로 감소하였으며, 또한 RAW 264.7 세포에 복합추출물을 처리하였을 경우 염증 매개 인자인 TNF-α, IL-6, PGE2 및 NO 생성량이 감소하였고, 이러한 염증 매개 인자 억제 효능은 복합추출물이 단독추출물보다 더 뛰어나게 억제하는 것을 확인하였다. 이러한 결과로 미루어볼 때 고욤잎, 감잎 및 뽕잎을 혼합한 복합추출물을 사용할 때 효능이 더 우수한 것을 확인하였고, 아토피 피부염 증상 개선 및 염증관련 질환 치료를 위한 기능성 천연물 소재 및 제품 개발에 응용이 가능할 것으로 생각한다. The present study investigated the anti-atopic effects of mixed extracts from date plum, persimmon, and mulberry leaves (DPME) on atopic dermatitis (AD)-like skin lesions in hairless mice. The in vivo results demonstrated that DPME treatment significantly reduced the dermatitis clinical score and epidermal thickness in AD-like skin lesions. Histological analyses showed that DPME treatment strongly inhibited dermal infiltration of inflammatory cells and activity of mast cells in AD-like skin lesions. DPME treatment inhibited production of serum IgE and interluekin (IL)-4 in hairless mice with AD. Moreover, DPME treatment significantly suppressed production of tumor necrosis factor (TNF)-α and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. In addition, DPME treatment reduced production of pro-inflammatory mediators (nitric oxide, prostaglandin E2, TNF-α, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Therefore, the results of this study indicate that the anti-atopic and anti-inflammatory effects of DPME may be involved in the regulation of inflammatory responses, suggesting that DPME may be used as an anti-atopic dermatitis material and natural anti-inflammatory ingredient.

Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation

Min Jin-Young,Kim Jin Youp,성충만,Kim Seon Tae,조현진,문수진,Cho Sung-Woo,Hong Sang Duk,Ryu Gwanghui,Cho Kyoung Rai,Kim Young Hyo,Park Soo-Kyoung,Kim Dong-Kyu,Lee Dong Hoon,Heo Sung Jae,Lee Ki-Il,Kim Su Jin,Le 대한천식알레르기학회 2023 Allergy, Asthma & Immunology Research Vol.15 No.4

Purpose: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters. Methods: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1β, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-β1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster. Results: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype. Conclusions: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

Lactic Acid Bacteria Improves Peyer`s Patch Cell-Mediated Immunoglobulin A and Tight-Junction Expression in a Destructed Gut Microbial Environment

( Sung Hwan Kim ),( Woonhee Jeung ),( Il Dong Choi ),( Ji Woong Jeong ),( Dong Eun Lee ),( Chul Sung Huh ),( Geun Bae Kim ),( Seong Soo Hong ),( Jae Jung Shim ),( Jung Lyoul Lee ),( Jae Hun Sim ),( Yo 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.6

To evaluate the effects of lactic acid bacteria (LAB) on Peyer`s patch cells, mice were treated with a high dose of kanamycin to disturb the gut microbial environment. The overarching goal was to explore the potential of LAB for use as a dietary probiotic that buffers the negative consequences of antibiotic treatment. In vitro, LAB stimulated the production of immunoglobulin A (IgA) from isolated Peyer`s patch cells. Inflammation-related genes (TNF-α, IL-1β, and IL-8) were up-regulated in Caco-2 cells stimulated with lipopolysaccharide (LPS), while tight-junction-related genes (ZO-1 and occludin) were down-regulated; the effects of LPS on inflammatory gene and tight-junction gene expression were reversed by treatment with LAB. Mice treated with a high dose of kanamycin showed increased serum IgE levels and decreases in serum IgA and fecal IgA levels; the number of Peyer`s patch cells decreased with kanamycin treatment. However, subsequent LAB treatment was effective in reducing the serum IgE level and recovering the serum IgA and fecal IgA levels, as well as the number of Peyer`s patch cells. In addition, ZO-1 and occludin mRNA levels were up-regulated in the ileum tissues of mice receiving LAB treatment. Lactic acid bacteria can enhance the intestinal immune system by improving the integrity of the intestinal barrier and increasing the production of IgA in Peyer`s patches. Lactic acid bacteria should be considered a potential probiotic candidate for improving intestinal immunity, particularly in mitigating the negative consequences of antibiotic use.

BER을 경감하기 위한 직접파와 지연파를 분리, 합성하는 시스템

洪性一,邊健植,鄭宗宇,朴在云 東亞大學校 附設 情報通信硏究所 1993 情報通信硏究所論文誌 Vol.1 No.1

본 논문에서는 다중 경로에 따른 수신신호의 노화, 특히 이동통신에 대해서 문제가 되는 페이딩 대책으로 직접파와 지연파를 분리, 합성하는 적응 배열 안테나 시스템을 제시하고 분리된 직접파 출력 또는 지연파 출력만을 이용하는 시스템보다 두 신호를 합성한 시스템의 BER이 개선됨을 제시하였다. 시뮬레이션을 행한 결과 적응 배열 안테나가 적절히 동작하는 상황에 대해서는 분리된 출력을 적응적 Weight 조정을 하여 합성함으로써 직접파만을 이용하는 것보다 오율이 향상됨이 확인되었다.

후두암에서의 인유두종 바이러스의 검출과 아형분류

선동일,김민식,조재홍,박영학,조승호 대한이비인후과학회 1998 대한이비인후과학회지 두경부외과학 Vol.41 No.5