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.

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)

HO-1 Induction by <i> Selaginella tamariscina</i> Extract Inhibits Inflammatory Response in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

Won, An-Na,Kim, Sun Ah,Ahn, Jung Yun,Han, Jae-Hyun,Kim, Chang-Hyun,Lee, Ju-Hee,Kim, Dong-Il Hindawi 2018 Evidence-based Complementary and Alternative Medic Vol.2018 No.-

<P><I>Selaginella Herba</I> is the dried, aerial part of<I> Selaginella tamariscina </I>(P.Beauv.) Spring and has been used to treat amenorrhea, abdominal pain, headaches, and hematuria in Korea. However, scientific evidence regarding the anti-inflammatory activity and action mechanism of<I> Selaginella tamariscina</I> is lacking. Thus, the present study was performed to investigate the anti-inflammatory and antioxidant activities of<I> Selaginella tamariscina</I> ethanol extract (STE) against lipopolysaccharide (LPS)-induced inflammatory responses and identify the molecular mechanism responsible. STE was prepared by heating in 70% ethanol and its quality was confirmed by HPLC. STE dose-dependently inhibited the productions of inflammatory mediators (NO and PGE<SUB>2</SUB>) and proinflammatory cytokines (IL-1<I>β</I> and IL-6) in LPS-stimulated RAW 264.7 cells. STE markedly suppressed the phosphorylations of MAPKs, I<I>κ</I>B-<I>α</I>, and NF-<I>κ</I>B and the nuclear translocation of NF-<I>κ</I>B induced by LPS stimulation. In addition, STE exhibited good free radical scavenging activity and prevented ROS generation by LPS. STE also upregulated the expression of Nrf2 and HO-1 and promoted the nuclear translocation of Nrf2. Taken together, STE was found to have anti-inflammatory and antioxidant effects on RAW 264.7 macrophages and the mechanism appeared to involve the MAPK, NF-<I>κ</I>B, and Nrf2/HO-1 signaling pathways. These results suggest that STE might be useful for preventing or treating inflammatory diseases and provide scientific evidence that supports the developments of herbal prescriptions or novel natural products.</P>

Renal Sympathetic Denervation Induces Acute Myocardial Inflammation through Activation of Caspase-1 and Interleukin-1β

Dong Won Lee(이동원),Il Young Kim(김일영),Ihm Soo Kwak(곽임수) 한국생명과학회 2018 생명과학회지 Vol.28 No.2

원심성, 구심성 교감신경 신호는 고혈압 및 심부전의 발생과 밀접한 관련이 있다. 혈관 내 카테터를 이용한 교감신경절제술(RDM)은 난치성 고혈압의 대체치료로 시행되어 왔다. 시술과 관련하여 장기간 신장의 안정성에 대해서는 보고가 있었으나 단기간 심근의 안정성에 대한 연구 결과는 없었다. 저자들은 RDN 시술로 인한 교감신경차단 후 염증성 심근손상이 발생할 수 있음을 가정하여 실험으로 검증하고자 하였다. 25마리의 암컷돼지를 3군으로 나누고–정상대조군(n=5), Sham군(n=5), RDN 시술군(n=15)–RDN 시술군을 시술 후 sacrifice 시기에 따라 다시 세분하였다–시술 후 즉시 sacrifice한 RDN-0 (n=5), 시술 1주 후 sacrifice한 RDN-1 (n=5), 시술 2주 후 sacrifice한 RDN-2 (n=5). 조영제의 영향을 배제하기 위해 설정했던 Sham군과 정상대조군 간에는 의미있는 차이를 보이지 않았다. IL-1β, TNF-α 등의 염증 싸이토카인은 시술 1주 후 증가하여 2주째 감소하였다. 항염증 싸이토카인 IL-10은 시술 직후부터 증가하여 2주째 감소하였다. Inflammasome에 의해 위험신호(danger signal)를 전달받고 활성화되는 Caspase-1 및 inflammasome을 매개하는 도메인 ASC는 시술 직후 활성화되어 발현이 증가하였고 2주까지 지속되었다. 그러나 caspase-1을 매개할 것으로 추정되었던 NLRP3 inflammasome의 발현은 의미있는 차이를 보이지 않았다. RDN 시술에 의한 교감신경차단은 caspase-1, IL-1β 등의 활성화에 의해 염증성 심근손상을 초래할 수 있으며 RDN 시술 후에는 그 위험성을 고려해야 하겠다. NLRP3 외에 다른 NLRP inflammasome pathway의 관련성에 대한 추가연구가 필요하다. Efferent and afferent sympathetic nerves are closely related to the development of hypertension and heart failure. Catheter-based renal sympathetic denervation (RDN) is implemented as a strategy to treat resistant hypertension. We investigated whether RDN procedure causes inflammatory damage on myocardium in the early phase of sympathetic denervation. Twenty-five female swine were divided into 3 groups: normal control (Normal, n=5), sham-operated control (Sham, n=5), and RDN groups (RDN, n=15). The RDN group was further subdivided into 3 subgroups according to the time of sacrifice: immediately (RDN-0, n=5), 1 week (RDN-1, n=5), and 2 weeks (RDN-2, n=5) after RDN. There were no significant changes in the clinical parameters between the normal control and sham-operated group using contrast-media. In the myocardium, inflammatory cytokines, IL-1β and TNF-α increased at the first week, and then decreased at the second week after RDN. Anti-inflammatory cytokine, IL-10 increased immediately, and then decreased at the second week after RDN. Caspase-1 activity and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression increased immediately after RDN until the second week. However, nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) expression did not show any significant differences among the groups. The RDN can cause acute myocardial inflammation through activation of caspase-1 and IL-1β. We should pay attention to protecting against early inflammatory myocardial damage after RDN.

The Effect of Human Placental Extract on Rheumatoid Arthritis in an Animal Model

Jeong Dong Park,신희석,Sang-Il Lee,A Ram Kim,Jong Moon Park,Sang-Yeop Shin,Jun Hwa Shin,Seung Won Moon,Hyun Park,오민균 대한재활의학회 2012 Annals of Rehabilitation Medicine Vol.36 No.2

Objective To assess the effi cacy of human placental extract (HPE) in an animal model of rheumatoid arthritis (RA). Method We used (i) KRN C57BL/6 TCR transgenic x NOD mice (KBx/N) serum transfer arthritis and (ii) collageninduced arthritis (CIA) mice to evaluate the effi cacy of HPE (1 ul or 100 ul, intra-peritoneal, three times per week)on RA. Incidence, severity of arthritis, and hind-paw thickness were quantifi ed. Joint destruction was analyzed using modifi ed mammographic imaging. Histopathological analysis for infl ammation, cartilage, and osteoclasts was performed using Hematoxylin-eosin (H-E), safranin-O, and tartrate-resistant acidic phosphatase (TRAP). ELISAs were used for detection of various cytokines in serum and joint tissue. Results Th ere were no signifi cant diff erences in incidence of arthritis, clinical scores of arthritis, and hind-paw thickness between HPE-treated and vehicle-treated groups for up to 2 weeks in the KBx/N serum transfer arthritis model. Histopathological analysis also showed no diff erences 2 weeks after treatment. Levels of TNF-α, IL-1β, IL-6, IL-10, and RANKL in serum and joint tissues were similar in all groups. Furthermore, there were no diff erences in clinical, radiological, and histological parameters between HPE-treated and vehicle-treated group for 3 weeks in the CIA model. Conclusion Systemic treatment with HPE has no benefi cial eff ects on arthritis in animal models of RA. Th erefore,indiscreet use of HPE in RA should be forbidden.

A hot-water extract of <i>Sanguisorba officinalis</i> ameliorates endotoxin-induced septic shock by inhibiting inflammasome activation : HSO attenuates inflammasome activation

Seo, Dong-Won,Cho, Yong-Il,Gu, Suna,Kim, Da-Hee,Yi, Young-Joo,Lee, Sang-Myeong Center for Academic Publications Japan 2018 Microbiology and immunology Vol.62 No.1

<P>The inflammasome is a multiprotein signaling complex that mediates inflammatory innate immune responses through caspase 1 activation and subsequent IL-1 secretion. However, because its aberrant activation often leads to inflammatory diseases, targeting the inflammasome holds promise for the treatment of inflammation-related diseases. In this study, it was found that a hot-water extract of Sanguisorba officinalis (HSO) suppresses inflammasome activation triggered by adenosine 5-triphosphate, nigericin, microbial pathogens, and double stranded DNA in bone marrow-derived macrophages. HSO was found to significantly suppress IL-1 production in a dose-dependent manner; this effect correlated well with small amounts of caspase 1 and little ASC pyroptosome formation in HSO-treated cells. The anti-inflammatory activity of HSO was further confirmed in a mouse model of endotoxin-induced septic shock. Oral administration of HSO reduced IL-1 titers in the serum and peritoneal cavity, increasing the survival rate. Taken together, our results suggest that HSO is an inhibits inflammasome activation through nucleotide-binding domain and leucine-rich repeat pyrin domain 3, nucleotide-binding domain and leucine-rich repeat caspase recruitment domain 4 and absent in melanoma 2 pathways, and may be useful for treatment of inflammasome-mediated diseases.</P>

CP-690550 Treatment Ameliorates Established Disease and Provides Long-Term Therapeutic Effects in an SKG Arthritis Model

Oh, Keunhee,Seo, Myung Won,Kim, In Gyu,Hwang, Young-Il,Lee, Hee-Yoon,Lee, Dong-Sup The Korean Association of Immunobiologists 2013 Immune Network Vol.13 No.6

Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-${\gamma}$, and IL-6 and increased level of immunoregulatory IL-10.

The Effects of Electro-Acupuncture the Rat with Induced MCAO

Jung-Hyun Choi,Ji-Sung Kim,Dong-Il Kim,Bo-Kyoung Kim,Soon-Hee Kim,Chi-Won Song 대한한의학회 2009 대한한의학회지 Vol.30 No.3

The Effects of Electro-Acupuncture the Rat with Induced MCAO

Choi, Jung-Hyun,Kim, Ji-Sung,Kim, Dong-Il,Kim, Bo-Kyoung,Kim, Soon-Hee,Song, Chi-Won The Society of Korean Medicine 2009 대한한의학회지 Vol.30 No.3

Objectives : This study was aimed at examining the effects of the application of EA (electroacupuncture) at GV20 and LI4 in the early cerebral ischemia on the size of cerebral infarction, COX-2 and IL-6. Methods : For this experiment, 21, six-week-old male S-D (Sprague - Dawley) rats weighting 160g to 200g were selected and randomly classified into 3 groups, seven rats in each group. Brain ischemia was simulated using a modified Koizumi method which was performed on each rat. In the GV20 group, the GV20 of the SD rats was stimulated for thirty minutes with acupunctural electrode low frequency stimulator five hours after inducement of ischemia. For the LI4 group, the LI4 was stimulated as above, while for the Ischemia group, no stimulation was applied. Twenty-four hours after the experiment, stained cerebral tissues were examined and an immuno-histological test was done to examine inflammatory reaction Results : Out of the three groups, the LI4 group showed the smallest size of cerebral infarction and the Ischemia group showed the highest COX-2 (cyclooxygenase-2) expression value in the cortex of the cerebrum. In addition, the LI4 group showed the lowest COX-2 expression value in unknown putamen out of the three groups. Conclusions : We infer that EA, applied at LI4 and GV20 in early ischemia, is effective in delaying the expression of IL-6 (interleukin-6) and COX-2, the inflammatory agents manifested from stroke. In addition, application at LI4, rather than GV20, can lower the expression value of the inflammatory agents. Further, EA can be an effective way to block early inflammatory reaction in stroke.

임신에 의한 비특이 세포성 면역의 변동

박현명,김춘추,김동집,김원일,조성훈,이준모,김승조 大韓血液學會 1984 大韓血液學會誌 Vol.19 No.2