한국 여성에서 자연 조기 분만과 Interleukin-1β 및 Interleukin-1 receptor antagonist 유전자 다형성의 연관성

김세련 ( Se Ryun Kim ),박영준 ( Young Jun Park ),류기영 ( Ki Young Ryu ),김종욱 ( Jong Wook Kim ),송은섭 ( Eun Seob Song ),이병익 ( Byung Ick Lee ) 대한산부인과학회 2007 Obstetrics & Gynecology Science Vol.50 No.1

Objective: Preterm birth is an important cause of infant death and morbidity but its pathophysiology still remains to be clear. The associations between preterm birth and the polymorphism of interleukin-1β gene and interleukin-1 receptor antagonist gene have been suspected. And ethnic variations in the polymorphism of the genes were also reported. We decided to study polymorphisms of interleukin-1β+3953 and interleukin-1 receptor antagonist in Korean pregnant women. Methods: Patients were divided into 2 groups. Group 1 is the control group of 33 subjects with uncomplicated term delivery : group 2 is the case group of patients who had spontaneous preterm delivery. Polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. Results: There were significant differences in gestational age and birth weight between two groups (P<0.001). No significant differences were found in genotypic frequencies and allelic frequencies in interleukin-1β+3953 between two groups. Interleukin-1 receptor antagonist gene had 5 alleles and the most frequent allele was IL1RN*1 (410bp), 66.7% in control group and 77.8% in case group. And significant differences were not found in genotypic frequencies and allelic frequencies between two groups, too. Conclusion: There were no significant differences in polymorphisms in interleukin-1β +3953 and interleukin-1 receptor antagonist between term delivery group and preterm birth group.

위암에서 Helicobacter pylori cagA 유전자와 숙주 Interleukin-1 Beta 및 Interleukin-1 수용체 길항제 유전자 다형성

이재승 ( Jae Seung Lee ),김광하 ( Gwang Ha Kim ),허정 ( Jeong Heo ),박도윤 ( Do Youn Park ),전은숙 ( Eun Sook Jun ),강대환 ( Dae Hwan Kang ),송근암 ( Geum Am Song ),조몽 ( Mong Cho ),양웅석 ( Ung Suk Yang ) 대한소화기학회 2003 대한소화기학회지 Vol.41 No.6

Background/Aims: Both Helicobacter pylori (H. pylori ) cagA genotype and host nterleukin-1 beta/interleukin-1 receptor antagonist (IL-1B/IL-1RN ) gene polymorphisms play a role in determining the clinical consequences of H. pylori infection. In this study, we investigated H. pylori cagA genotype and host IL-1B /IL-1RN polymorphisms in Korean patients to clarify their involvement in the occurrence of gastric carcinoma. Methods: The population comprised of 134 patients with H. pylori infection: 82 with gastric carcinoma and 52 with gastritis. The DNA was isolated from gastric biopsy sample and H. pylori cagA genotype was determined by PCR. The IL-1B ?11 polymorphism was genotyped by PCR-RFLP and the IL-1RN polymorphism was analyzed. Results: Infection with cagA+ H. pylori was not associated with an increased risk for gastric carcinoma. The IL-1B -511 *T carriers and IL-1RN *2 carriers did not show an increased risk for gastric carcinoma. Combining bacterial/host genotypes, cagA+ /IL-1B -511 *T carriers and cagA+ /IL-1RN *2 carriers showed no increased risk of gastric carcinoma. Classifying of gastric carcinoma into intestinal and diffuse type, the bacterial/host genotypes were also not associated with increased risk of each type. Conclusions: Combined H. pylori cagA gene and host IL-1B /IL-1RN polymorphisms showed no increased risk of gastric carcinoma. Therefore, it seems other endogenous or exogenous factors might play more important roles in the development of gastric carcinoma in Korean. (Korean J Gastroenterol 2003;41:438-446)

Interleukin-1β에 의하여 치주인대세포에서 유리된 cytokine이 파골세포형성에 미치는 영향

이종갑,곽월아,유윤정,이승일,김태선 大韓小兒齒科學會 1996 大韓小兒齒科學會誌 Vol.23 No.1

Tooth movement is induced by bone remodeling during orthodontic treatment. Bone remodeling is regulated by various cytokines. Especially interleukin-1 (IL-1β), a cytokine present in periodontal ligaments of experimentally moved teeth, elicits bone resorption. In these processes, IL-1-induced bone resorption is mediated by interleukin-6 (IL-6) and granulocyte macrophage-colony stimulating fector (GM-CSF) secreted from osteoblasts. Periodontal ligament cells, which function as an anchorage for tooth, lie between alveolar bone and cementum. Therefore cytokines produced in the periodontal ligament (PDL) cells may also directly affect alveolar bone resorption in orthodontic tooth movement. Here I have examined whether PDL cells express IL-1β,interleukin-6 (IL-6) and granulocyte macrophage-colony stimulating factor (GM-CSF) mRNA and secrete those cytokines in response to IL-1β. Finally I have investigated whether IL-6 produced from PDL cells induces osteoclast formation in mouse bone marrow cell cultures. The expression of mRNA was estimated by polymerase chain reaction (PCR). The concentration of cytokines was quantified using enzyme linked immunosorbent method and the osteoclasts in bone marrow cultures were identified by tartrate resistant acid phosphatase (TRAP) stain. As results of these studies, IL-1βstimulated the expression of IL-1β, IL-6 and GM-CSF mRNA in PDL cells. 0.05 ng/ml IL-1βalso induced maximum production of Il-6 and GM-CSF in these cells. After an addition of IL-1β(0.05 ng/ml), IL-6 production increased from 2 hours to 8 hours and GM-CSF production also increased from 4 hours to 8 hours. IL-6 (100 ng/ml) increased the number of TRAP positive multinucleated cells in the presence of soluble interleukin-6 receptor (sIL-6R, 100 ng/ml). These results suggest that IL-1βmay stimulate alveolar bone resorption by inducing IL-6 and GM-CSF production in PDL cells which enhance osteoclast differentiation and IL-6 enhances osteoclast formation in the presence of sIL-6R. And this process by IL-1βmay be closely associated with alveolar bone resorption induced by orthodontic force.

치수및 치근단병소에서 interleukin-1α, interleukin-1β, tumor necrosis factor-α의 분포에 관한 연구

고현정,정관희,임성삼 大韓齒科保存學會 1998 Restorative Dentistry & Endodontics Vol.23 No.1

This study was designed to examine the tissue levels of interleukin-1α(IL-1α), interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in inflamed human dental pulps and periapical lesions, and to determine the relationship between each cytokine and pulpal and periapical pathosis. The pulps used in this experiment, were obtained in routine endodontic treatment and the periapical lesions in periapical surgery after clinical diagnoses were performed. These specimens were divided into four groups as normal pulp group(control group, n=9), acute pulpitis group(n=9), chronic pulpitis group(n=10) and periapical lesion group(n=18) and stored in liquid N_2. For extract preparation, tissues were finely minced with a scalpel, and the fragments were incubated in 0.5㎖ homogenizing buffer (0.1 mol/L potassium chloride, 0.02 mol/L TRIS; pH=7.6) for two hours and grinded with glass homogenizer. Debris was removed by centrifugation and supernatants were immediately tested with enzymelinked immunosorbent assay(ELISA, R&D Co., Minneapolis, USA). Following results were obtained ; 1. The concentrations of IL-1α in all experimental groups were significantly higher than in control group(p<0.05). And the concentrations of IL-1α in periapical lesion group were somewhat higher than in two pulpitis groups, but the differences among those groups were not stastically significant(p>0.05). 2. The concentrations of IL-1β in all experimental groups were significantly higher than in control group(p<0.05), and all the experimental groups expressed similar concentrations. 3. The concentrations of TNT-α in all experimental groups were higher than in control group but only the differences between chronic pulpitis group and control group were statistically significant(p<0.05). And the concentrations of TNT-α in acute and chronic pulpitis groups were higher than in periapical lesion group but only the differences between chronic pulpitis group and periapical lesion group were statistically significant(p<0.05). 4. There was significant correlation only between IL-1α and IL-1β in periapical lesion group(p<0.05).

Interleukin-1β 유전자 내 -511C/T 단일염기다형성과 유방암 관련 우울증

김재민,강희주,장지은,김선영,김성완,신일선,박민호,윤정한,윤진상 대한우울조울병학회 2011 우울조울병 Vol.9 No.3

Objectives : Pro-inflammatory cytokines are related to the pathophysiology of both cancer and depression, and their secretion is controlled by the transcriptional activity of particular gene polymorphisms. This study aimed to investigate whether interleukin (IL)-1β -511C/T gene polymorphism is associated with depression following mastectomy for breast cancer. Methods : A total of 309 patients with breast cancer were evaluated one week after mastectomy, and 244 (79%) were followed one year later. Depression (major+minor depressive disorders) was diagnosed according to DSM-IV criteria using the Mini International Neuropsychiatric Interview, and classified into prevalent, persistent, and incident depression. Associations of IL-1β -511C/T polymorphism with the three depressive status were estimated using logistic regression models. Results : At baseline, 74 (24%) patients were classified with prevalent depression ; and at follow up, 19 (8%) and 25 (10%) patients were classified with persistent and incident depression, respectively. The IL-1β -511T/T genotype was independently associated with prevalent and persistent depression, but not with incident depression. Conclusion : IL-1β -511T/T genotype may involve in the etiology of depression occurring in women with breast cancer who receive a mastectomy. (J of Kor Soc for Dep and Bip Disorders 2011;9:189-193)

Association Analysis of Interleukin-1β, Interleukin-6, and HMGB1 Variants with Postictal Serum Cytokine Levels in Children with Febrile Seizure and Generalized Epilepsy with Febrile Seizure Plus

최지은,최선아,김수연,김헌민,임병찬,황희,채종희,김기중,오소희,김은영,신전수 대한신경과학회 2019 Journal of Clinical Neurology Vol.15 No.4

Background and Purpose Febrile seizure (FS) is a unique type of seizure that only occurs during childhood. Genelized epilepsy with febrile seizure plus (GEFS+) is a familial epilepsy syndrome associated with FS and afebrile seizure (AFS). Both seizure types are related to fever, but whether genetic susceptibility to infammation is implicated in them is still unclear. To analyze the associations between postictal serum cytokine levels and genetic variants in the cytokine genes interleukin (IL)-1β, IL-6, and high mobility group box-1 (HMGB1) in FS and GEFS+. Methods Genotyping was performed in 208 subjects (57 patients with FS, 43 patients with GEFS+, and 108 controls) with the SNaPshot assay for IL-1β-31 (rs1143627), IL-1β-511 rs16944), IL-6-572 (rs1800796), and HMGB1 3814 (rs2249825). Serum IL-1β, IL-6, and HMGB1 levels were analyzed within 2 hours afer seizure attacks using the ELISA in only 68 patients (38 FS, 10 GEFS+, and 20 controls). Te allele distribution, genotype distribution, and correlations with serum cytokine levels were analyzed. Results Near-complete linkage disequilibrium exists between IL-1β-31 and IL-1β-511 variants. CT genotypes of these variants were associated with signifcantly higher postictal serum IL-1β levels than were CC+TT genotypes in FS (both p<0.05). CT genotypes of IL-1β-31 and IL-1β-511 variants were more strongly associated with FS than were CC+TT genotypes (odds ratio=1.691 and 1.731, respectively). For GEFS+, serum IL-1β levels afer AFS for CT genotypes of IL-1β-31 and IL-1β-511 were also higher than for CC+TT genotypes. No signifcant associations were found for IL-6 and HMGB1. Conclusions Genetic variants located in IL-1β-31 and IL-1β-511 promotor regions are correlated with higher postictal IL-1β levels in FS. Tese results suggest that IL-1 gene cluster variants in IL-1β-31 and IL-1β-511 are a host genetic factor for provoking FS in Korean children.

Interleukin-1β induces bone resorption by regulation of prostaglandin E₂ synthesis and plasminogen activator activity, and TGF-β inhibits bone resorption of rat bone cells

Kim, Young-Hun,Lee, Young-Jun,Chung, Kyu-Rhim,Park, Young-Guk 대한치과교정학회 2000 대한치과교정학회지 Vol.30 No.6

골세포는 골대사에 영향을 미치는 다양한 성장인자와 싸이토카인을 생성하여 골 기질로 유리시킨다. 이 연구는 쥐의 장골 세포 배양 모델에서 recombinant human IL-1β가 PGE2 합성과 plasminogen activator의 활성 조절을 통한 골흡수 유도 기전의 일단을 구명하고, 이와 동시에 TGF-β에 의한 골흡수 억제 기전을 해명하는데 그 목적이 있다. 쥐의 장골 세포를 배양하여 통법의 골모세포 phenotype을 발현하는 세포를 분리하고 세포 배양능, alkaline phosphatase assay, PG assay, 골흡수능 측정들을 시행하여 다음의 결과를 얻었다. 1.IL-1β는 쥐의 골모세포의 증식, PGE2 생성 및 palsmonogen activator의 활성을 촉진하였다. 2.IL-1β는 쥐의 골모세포에서의 alkaline phosphatase 활성을 감소시켰다. 3.rhIL-1β는 골 흡수를 촉진시켰다. 4.TGF-β는 쥐의 장골 세포에서 골의 흡수를 억제하였으며, Vitamin D3에 의하여 유도된 골 흡수를 억제하였다. 이상의 연구 결과는 IL-1β에 의한 골 파괴의 병인과 관련하여 골 세포 대사의 병리학적 조절에 있어서의 IL-1β의 역할을 지지하며, 이와 동시에 골 흡수 억제에 있어서의 TGF-β의 역할을 확인시켜주는 것으로 생각된다. Bone cells produce multiple growth factors and cytokines that hale effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-β (TGF-β) or interleukin-1β (rhIL-1β) and bone cells in a rat long bone culture model. IL-1β regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-1β stimulated cellular proliferation as well as the synthesis of prostaglandin E2 and plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-β is present in the bone matrix and potentially released during bone resorption. TGF-β reduced basal bone resorption and inhibited vitamin D3 [1,25(OH)2D3]-Induced bone resorption in rat long bone cells. These results support the role of IL-1β in the pathological modulation of bone cell metabolism, with regard to implication in the pathogenesis of osteoporosis by IL-1β, and that TGF-β positively inhibits the bone resorption.

Cytokine interleukin-1β로 誘發된 糖尿病 마우스의 膵臟 glucokinase 및 hexokinase 活性에 對한 五倍子의 效果에 關한 硏究

최형일,정지천,김철호 동국대학교 한의학연구소 1998 東國韓醫學硏究所論文集 Vol.7 No.1

Glucokinase와 hexokinase는 간과 췌장에서 인슐린에 의해 혈당이용을 증대시키며 혈당농도를 감지하여 인슐린 분비를 조절하는 효소로서 인슐린비의존성당뇨병(NIDDM)의 병인과 밀접한 관계가 있는 효소이다. Cytokine의 일종인 interleukin-1β (IL-1β)는 췌장 도세포에서의 인슐린 분비와 β-cell에 대한 세포 독성을 효과적으로 조절하여 장기간 노출시키면 인슐린 분비와 생합성을 저해하며 β-cell을 파괴하여 β-cell의 기능적, 구조적 손상을 초래하여 IDDM을 유발한다. 본 연구에서는 당뇨병 치료의 전통한방약제로서 사용되고 있는 五倍子추출물의 효과를 해명하기 위하여 IL-1β유발 실험적 당뇨마우스의 glucokinase와 hexokinase의 활성을 검토한 결과, lL-1β주사에 의해 체중과 공복시의 glucose 및 insulin 분비가 증가되었으나, 五倍子투여로 공복시의 insulin분비가 감소하였으며 체중과 공복시의 혈당은 유의성은 없었으나 대조군에 비하여 감소하였다. 그러나, 혈당수치가 정상군에 비하여 현저하게 증가되었으나 五倍子투여로 현저히 감소하였으며 Insulin치의 상승과 분비지연도 五倍子투여군에서는 정상군과 유사한 경향을 보였다. 한편, 혈중 glucokinase와 hexokinase의 활성은 IL-1β주사에 의해 현저히 감소되었으나, 五倍子 투여로 유의성 있게 상승되었다. 이상의 결과로, 五倍子는 IL-1β로 유발된 실험적 당뇨병에서 포도당인산화 효소인 glucokinase와 hexokinase의 활성을 증가시키는 것으로 나타났다. We investigated the in vivo effect of an aquous extract from Rhois Galla (R-G) on glucokinase and hexokinase activities of diabetes mellitus induced by interleukin-β (IL-1β). After 1 week of alloxan injection, the levels of serum glucose and insulin secretion were dramatically increased, however, the insulin secretion was decreased with administration of R-G, IL-1β injection allowed the scrum glucose level increased and the level was decreased by R-G administration. Furthermore, we could observe that R-G was effective in recovering the levels of insulin secretion. Enzyme activities of the gtucokinase and hexokinase were decreased by IL-1β treatment. In contrast, R-G administration to the mice allowed proportion increasing. Seemingly, when IL-1β was injected to the mice, enzyme activities of the glucokinase and hexokinase were decreased. But, R-G stimulated induction of enzyme activities of the glucokinase and hexokinase as high as normal group. These results suggested that R-G is highly effective in treatment of diabetes mellitus.

Synergy between adiponectin and interleukin-1β on the expression of interleukin-6, interleukin-8, and cyclooxygenase-2 in fibroblast-like synoviocytes

이연아,Hyun Mi Choi,이상훈,양형인,유명철,홍승재,김경수 생화학분자생물학회 2012 Experimental and molecular medicine Vol.44 No.7

To determine whether adiponectin may have synergistic effects in combination with the proinflammatory cytokine interleukin (IL)-1β regarding the production of proinflammatory mediators during arthritic joint inflammation,synovial cells from rheumatoid arthritis (RA) patients were treated with adiponectin, IL-1β, and their combination for 24 h. Culture supernatant was collected and analyzed by enzyme-linked immunosorbent assay for levels of IL-6, IL-8, prostaglandin E2 (PGE2), vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs). Adiponectin-mediated intracellular signaling pathways were investigated to elucidate the molecular mechanisms underlying their synergy. The association of proinflammatory mediators with adiponectin was investigated in the synovial fluid of arthritis patients. Adiponectin functioned synergistically with IL-1β to activate IL-6, IL-8, and PGE2 expression in RA fibroblast-like synoviocytes; Levels of VEGF, MMP-1,and MMP-13 were not synergistically stimulated. Adiponectin and IL-1β each increased the expression of both adiponectin receptor 1 and IL-1 receptor 1. However, adiponectin and IL-1β did not synergistically support the degradation of IκB-α or the nuclear translocation of NF-κB. Synergistically increased gene expression was significantly inhibited by MG132, an NF-κB inhibitor. Supporting the in vitro results, IL-6and IL-8 levels were positively associated with adiponectin in synovial joint fluid from patients with RA, but not osteoarthritis (OA). In conclusion, adiponectin and IL-1β may synergistically stimulate the production of proinflammatory mediators through unknown signaling pathways during arthritic joint inflammation. Adiponectin may be more important to the pathogenesis of RA than previously thought.

신생아 폐혈증에서 Cytokine치들의 의의

박혜진,김소연,이준화,최은진,김진경,김상경,정혜리,김우택 대한소아과학회 2004 小兒科 Vol.47 No.5