이질아메바에 의한 인체 대장상피세포주 HT-29에서의 interleukin-8 유전자의 발현

김정목,정현채,임경일,조양자,김정룡 INSTITUTE OF TROPICAL MEDICINE YONSEI UNIVERSITY 1995 YONSEI REPORTS ON TROPICAL MEDICINE Vol.26 No.1

이질아메바에 의한 장염 환자의 조직 또는 이질아메바를 실험적으로 감염시킨 동물의 조직 검사에서 호중구의 침윤이 특징적으로 관찰된다. 그러나 이와같은 호중구의 침윤을 설명할 수 있는 기전에 대한 연구는 매우 미흡하다. 따라서 본 연구자들은 아메바 감염 초기에 인체 대장상피세포에서 interleukin-8(IL-8)이 유도되어 호중구 침윤과 같은 염증반응이 유발될 것이라는 가설을 설정하였다. 이를 위하여 인체 대장상피세포주인 HT-29에 이질아메바 영양형을 실험적으로 노출시킨 뒤 발현되는 IL-8 mRNA를 역전사 중합효소법(reverse transcriptional polymerase chain reaction, RT-PCR)으로 검사함과 동시에 발현된 IL-8 mRNA를 인공적으로 합성시킨 표준 RNA와 RT-PCR법을 이용하여 정량하였다. 실험 결과 이질아메바 영양형에 노출된 30분 후 부터 IL-8 mRNA가 발현되기 시작하였다. 그리고 그 발현 분자수는 노출 시간의 증가에 따라 계속 증가하여 3시간 대에는 3.1×10(7) molecules/㎍ total RNA를 나타내었다. 동시에 IL-8 mRNA의 발현은 노출시킨 이질아메바 영양형의 수에 비례하였다. 즉, HT-29/아메바 영양형의 비율이 10:1인 경우 IL-8 mRNA의 발현 분자수는 1.2×10(7) molecules/㎍ total RNA로 나타났다. 이와같은 IL-8 mRNA의 발현은 IL-8 단백질 분비로 이어짐을 ELISA 검사로 확인할 수 있었다. 한편 이질아메바 파쇄액(lysate)도 대장상피세포주인 Caco-2에서 IL-8 mRNA발현을 유도하였다. 결론적으로 본 실험은 이질아메바 감염 초기에 대장상피세포로 부터 IL-8이 발현되며 이에 의하여 염증반응이 촉발될 가능성이 있음을 시사해 준다. The protozoan parasite, Entamoeba histolytica, is one of major causative agents of intestinal disease all over the world. In acute experimental infection, the early host response to E. histolytica is characterized by an infiltration of neutrophils. However, the chemotactic signal for this response is not well known. Based on the finding that human epithelial cells produce the potent neutrophil chemoattractant and activator, interlukin-8 (IL-8), IL-8 gene expression was examined thoroughly in human colon epithelial cells exposed to E. histolytica trophozoites. Cellular RNAs were extracted from HT-29 or Caco-2 human colon epithelial cells exposed to E. histolytica trophozoities for 30 minutes. 1 and 3 hours. IL-8 mRNA transcripts were measured by reverse transcriptional polymerase chain reaction (RT-PCR) using synthetic standard RNA. The number of IL-8 mRNA molecules increased from 30 minutes to 3 hours of exposure period, reaching 3.1×10(7) molecules/㎍ of total RNA. Expression pattern of IL-8 mRNA transcripts was parallel to the amounts of IL-8 protein measured by enzyme-linked immunosorbent assay (ELISA). Lysates of E. histolytica also induced expression of mRNA for IL-8 in colon epithelial cells. These results suggest that acute inflammatory reaction by E. hisstolytica may be initially triggered by proinflammatory cytokines such as IL-8 secreted from epithelial cells of the colon.

인간 재조합 인터루긴-32 면역조절작용에 대한 유세포 분석

이광수,김영관,채정일,심정현,김은미,강형식,김수현,윤도영,명평근 충남대학교 생물공학연구소 2006 생물공학연구지 Vol.12 No.-

Xenotransplantation of porcine organs has the potential to overcome the severe shortage of human tissues and organ available for human transplantation. however, it remains various hurdles for clinical xenotransplantation. In pig and mouse xenotransplantation, porcine xenograft evoke a strong cellular rejection response in immunocompetent host and grafts are destroyed within a week. This cellular immune response could involved both T cells and NK cells. A number of groups have shown that human NK cells can recognize and damage porcine endothelial cells. In addition, human T cells can respond to porcine endothelial cells through both direct and indirect mechanisms. Cellular rejection of porcine tissues requires T cells, particularly CD4^(+) cells. A new cytokine recombinant human interleukin-32α,β(IL-32α,β) has a role innate and acquired immune system. In order to investigate the role of recombinant mouse IL-18 and recombinant human IL-32α,β in xenograft rejection, we transplanted the PK(15) cells to C57BL/6 mice with or without intraperitoneal injection of recombinant mouse IL-18 or recombinant human IL-32 α,β. It was analyzed the population of NK cell, T cell and B cell in the C57BL/6 mice transplanted with PK(15) cells and recombinant mouse IL-18 or recombinant human IL-32α,β by flow cytometry analysis. As a result, lymph node and thymus of PK15/IL18, PK15/IL32α and PK15/IL32β injected group were increased to T cell activation population than normal injected groups. CD8^(+) T cells were decreased in lymph node of PK15/IL18, PK15/IL32α and PK15/IL32β injected groups. CD4^(+) T cells were increased in lymph node cell of PK15/IL32α and PK15/IL32β injected group and also, B cell population were increased in lymph node cell and spleen of PK15/IL18, PK15/IL32α and PK15/IL32β injected group. Therefore, we suggest that recombinant mouse IL-18 and recombinant human IL-32α,β suppress xenograft rejection in cellular xenotransplantation.

Prevalence and Risk Factors of Atrophic Gastritis and Intestinal Metaplasia in a Korean Population Without Significant Gastroduodenal Disease

Kim, Nayoung,Park, Young Soo,Cho, Sung-Il,Lee, Hye Seung,Choe, Gheeyoung,Kim, In Wook,Won, Yoo-Deok,Park, Ji Hyun,Kim, Joo Sung,Jung, Hyun Chae,Song, In Sung Wiley (Blackwell Publishing) 2008 Helicobacter Vol.13 No.4

<P>BACKGROUND AND AIM: The prevalence of gastric cancer and Helicobacter pylori infection is unacceptably high in Korea. This study was performed to evaluate the prevalence of atrophic gastritis (AG) and intestinal metaplasia (IM) and to identify their risk factors with respect to H. pylori virulence factors, and environmental and host factors, in Korean population without significant gastroduodenal disease. METHODS: The study cohort consisted of 389 subjects (> or = 16 years). AG and IM were scored histologically using the Sydney classification in the antrum and body, respectively. Prevalences and bacterial factors (i.e. cagA, vacA m1, and oipA), environmental factors (i.e. smoking and alcohol), and host factors (i.e. genetic polymorphisms of IL-1B-511, IL-1RN, TNF-A-308, IL-10-592, IL-10-819, IL-10-1082, IL-8-251, IL-6-572, GSTP1, p53 codon 72, and ALDH2) were evaluated. RESULTS: Prevalences of AG in the antrum and body were 42.5% and 20.1%, and those of IM were 28.6% and 21.2%, respectively. The presences of AG and IM were significantly higher in H. pylori-positive than in the H. pylori-negative subjects. Multivariate analysis showed that the risk factors for AG were H. pylori infection, age > or = 61 years, and cagA and vacA m1 positivity. For IM the risk factors were H. pylori infection, age > or = 61 years, a smoking history (rather than current smoking), strong spicy food, occupation (unemployed or nonprofessional vs. professional), and the presence of IL10-592 C/A as opposed to A/A. In addition, IL6-572 G carrier was found to have a protective effect against IM development as compared with C/C. CONCLUSION: H. pylori infection was most important risk factor of AG and IM. Bacterial factors were found to be important risk factor for AG but environmental and host factors were more important for IM.</P>

Free Paper Session : Upper Gastrointestinal Tract 1 ; Prevalence And Risk Factors For Atrophic Gastritis And Intestinal Metaplasia

( Na Young Kim ),( Dong Ho Lee ),( Joo Sung Kim ),( Hyun Chae Jung ),( In Sung Song ),( Kyung Phil Kang ),( Jung Hoon Lee ),( Jae Il Chung ),( Hyun Cheul Choi ),( Taek Man Nam ),( Sang Hyup Lee ),( Yo 대한소화기학회 2007 SIDDS Vol.9 No.-

Background/Aims: The prevalence of gastric cancer and Helicobacter pylori (Hp) infection is high in Korea. This study was performed to evaluate the prevalence rate of atrophic gastritis (AG) and intestinal metaplasia (IM) and their risk factors in the aspect of Hp virulence factors, environmental and host factors in normal population. Methods: The subjects consisted of 389, 135 H. pylori-negative and 254 H. pylori-positive. AG and IM were scored histologically by the Sydney classification in the antrum and body, respectively. Prevalence rate and bacterial factors such as cagA, vacA m1, m2, and oipA; environmental factors such as smoking, alcohol drinking; host factors such as genetic polymorphisms for IL-IB-511, IL-IRN, TNF-A, IL-10-592, IL-10-819, IL-10-1082, IL-8-251, IL-6-572, GSTP1, and p53 codon 72 were evaluated. Risk factors were calculated by multiple logistic regression analysis. Results: The prevalence rate of AG increased from 25%, 0% in the age of 20s, 45% and 22% in the 40s and 50% and 35% in the over 70s in the antrum and body, respectively (p<0.001). In case of IM it increased from 11.1% and 6.4% in the 30s up to 43% and 43% in over 70s in the antrum and body, respectively, (p<0.001). The positive rates of AG and IM were significantly higher in the Hp-positive than in the Hp-negative subjects. Multivariate analysis showed that the risk factors for AG were Hp infection, age ≥60, cagA and vacA m1 positive. In case of IM the risk factors were Hp infection, age ≥60, smoking, spicy food, occupation (unemployed or non professional vs. professional), IL6-572 G carrier over C/C and IL10-592 C/A vs. A/A. Conclusions: The prevalence rate of AG and IM increased proportional to age. The most risk factor for AG and IM was Hp infection. Bacterial factors were important for AG but environmental and host factors were rather important in case of IM.

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.

Effect of Cytokines and bFGF on the Osteoclast Differentiation Induced by 1α,25-(OH)<SUB>2</SUB>D<SUB>3</SUB> in Primary Murine Bone Marrow Cultures

Han-Jung Chae,Jang-Sook Kang,Byung-Gwan Bang,Seoung-Bum Cho,Jo-IL Han,Joo-Young Choi,Hyung-Min Kim,Soo-Wan Chae,Hyung Ryong Kim 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.6

<P> Bone is a complex tissue in which resorption and formation continue throughout life. The bone tissue contains various types of cells, of which the bone forming osteoblasts and bone resorbing osteoclasts are mainly responsible for bone remodeling. Periodontal disease represents example of abnormal bone remodeling. Osteoclasts are multinucleated cells present only in bone. It is believed that osteoclast progenitors are hematopoietic origin, and they are recruited from hematopoietic tissues such as bone marrow and circulating blood to bone. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells produce cytokines that can affect osteoclast formation. In vitro model systems using bone marrow cultures have demonstrated that IL-1β, IL-3, TNF-α, bFGF can stimulate the formation of osteoclasts. In contrast, IL-4 inhibits osteoclast formation. Knowledge of cytokines and bFGF that affect osteoclast formation and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as periodontal disease, osteoporosis and Paget s disease.

UVB-dependent inhibition of lipin-1 protects against proinflammatory responses in human keratinocytes

Minjung Chae,Eui-dong Son,Il-Hong Bae,조은경,Hyoung-June KIM,Ji-Yong Jung 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

Lipin-1 is an Mg2+-dependent phosphatidate phosphatase (PAP1) that catalyzes a critical step in the synthesis of glycerophospholipids and is also a cotranscriptional regulator. The role of lipin-1 in the regulation of inflammatory responses has been extensively studied in various cell types but not in skin cells. In the present study, the function of lipin-1 in UVB-induced proinflammatory responses was assessed in normal human epidermal keratinocytes (NHEKs). UVB radiation downregulated lipin-1 expression. Lipin-1 inhibition was mediated by UVB-dependent sterol-response element binding protein-1 (SREBP-1) inhibition. The UVB-dependent inhibition of lipin-1 and SREBP-1 was mediated by AMPK activation. UVB-induced activation of JNK was dependent on AMPK activation and mediated lipin-1 inhibition. Prevention of UVB-mediated lipin-1 repression by introducing a lipin-1 expression vector stimulated IL-6 and IL-8 production, suggesting that lipin-1 inhibition attenuates UVB-induced IL-6 and IL-8 production. The downregulation of lipin-1 ameliorated UVB-induced NF-ĸB phosphorylation, which might be attributed to the suppression of UVB-induced accumulation of free fatty acids (FFAs). Pharmacological inhibition of PAP1 with propranolol suppressed UVB-induced production of IL-6 and IL-8 in NHEKs and reconstituted human skin models. Taken together, lipin-1 is downregulated by exposure to UVB radiation, which confers protection against UVB-induced proinflammatory responses; therefore, the inhibition of lipin-1 is a potential strategy for photoaging.

Adrenomedullin inhibits IL-1관-induced rheumatoid synovial fibroblast proliferation and MMPs, COX-2 and PGE2 production.

Lee, Eun-Gyeong,Lee, Sang-Il,Chae, Han-Jung,Park, Seoung Ju,Lee, Yong Chul,Yoo, Wan-Hee Kluwer Academic/Plenum Publishers 2011 INFLAMMATION Vol.34 No.5

<P>To determine the effects of adrenomedullin (AM) on interleukin (IL)-1관-induced proliferation of rheumatoid synovial fibroblasts (RASFs) and production of matrix metalloproteinases (MMPs), cyclooxygenase (COX) and prostaglandin E2 (PGE2) by RASFs. The RASFs proliferation was evaluated with CCK-8 reagent in the presence of IL-1관 with/without AM (1-52) and AM inhibitor (AM (22-52)). MMPs, tissue inhibitor of metalloproteinase (TIMP-1), COXs, PGE2 and intracellular mitogen-activated protein kinase (MAPK) signalings, including p-ERK, p-p38, p-JNK were examined by immunoblotting or semiquantitative RT-PCR and ELISA. AM (1-52) inhibited IL-1관-induced RASFs proliferation and inhibited MMP-1, 3, COX-2 and PGE2 production. AM (1-52) also inhibited IL-1관-induced phosphorylation of ERK-1/2, p38, JNK. AM 22-52 inhibited the effects of AM (1-52) on proliferation of RASFs and production of MMP-1, 3, COX-2 via MAPKs. These results suggest that AM might involved joint destruction in rheumatoid arthritis and indicate that it might be a new therapeutic modality for management of this disease.</P>

한국인 직무 스트레스 측정도구의 개발 및 표준화

장세진,고상백,강동묵,김성아,강명근,이철갑,정진주,조정진,손미아,채창호,김정원,김정일,김형수,노상철,박재범,우종민,김수영,김정연,하미나,박정선,이경용,김형렬,공정옥,김인아,김정수,박준호,현숙정,손동국 大韓産業醫學會 2005 대한직업환경의학회지 Vol.17 No.4

Background and Purposes: Over the past three decades, numerous studies performed in Korea have reported that job stress is a determinant risk factor for chronic diseases and work disability. Every society has its own culture and occupational climate particular to their organizations, and hence experiences different occupational stress. An occupational stress measurement tool therefore needs to be developed to estimate it objectively. The purpose of this study is to develop and standardize the Korean Occupational Stress Scale (KOSS) which is considered to be unique and specific occupational stressors in Korean employees. Subjects and Methods: Data were obtained from the National Study for Development and Standardization of Occupational Stress (NSDSOS Project: 2002-2004). A total of 12,631 employees from a nationwide sample proportional to the Korean Standard Industrial Classification and the Korean Standard Occupational Classification were administered. The KOSS was developed for 2 years (2002-2004). In the first year, we collected 255 items from the most popular job stress measurement tools such as JCQ, ERI, NIOSH and OSI, and 44 items derived from the a qualitative study (depth interview). Forty-three items of KOSS, in the second year, were retained for use in the final version of the KOSS by using Delphi and factor analysis. Items were scored using conventional 1-2-3-4 Likert scores for the response categories. Results: We developed eight subscales by using factor analysis and validation process: physical environment (3 items), job demand (8 items), insufficient job control (5 items), interpersonal conflict (4 items), job insecurity (6 items), organizational system (7 items), lack of reward (6 items), and occupational climate (4 items). Together they explained 50.0% of total variance. Internal consistency alpha scores were ranged from 0.51 to 0.82. Twenty-four items of the short form of the KOSS (KOSS-SF) were also developed to estimate job stress in the work setting. Because the levels of the subscales of occupational stress were gender dependent, gender-specific standard norms for both the 43-item full version and the 24-item short form using a quartile for the subscales of KOSS were presented. Conclusion: The results of this study suggest that KOSS might be an appropriate measurement scale to estimate occupational stress of Korean employees. Further and more detailed study needs to be conducted to improve the validity of this scale.

폐경 후 여성에서 체성분과 골밀도와의 관계

채진욱,김일희,권우성,이근미,정승필,문용 영남대학교 의과대학 2003 Yeungnam University Journal of Medicine Vol.20 No.1

Background: Body weight is an important factor that influence the bone density in postmenopausal women except estrogen dificiency. However, different results are reported about the relationship between body composition and bone density in the postmenopausal women. We have studied the relationship between age, body weight, body mass index (BMI), waist hip ratio (WHR), muscle mass, fat mass, fat free mass and bone density. Materials and Methods: We have studied 127 persons of postmenopausal women who visited university medical center and examined the inbody 3.0 and Dual Energy X-ray Absorptiometry (DEXA) from Jan, 2001 to Jun, 2002. they didn't have any disease and didn't received homone therapy, osteoprosis therapy or other medication that influence the bone density. Results: The numbers of study subjects is total 127 persons. Mean age is 56.9±5.14, mean weight is 59.3±8.7 kg, mean BMI is 25.37±3.16 (kg/㎡), mean fat mass is 20.02±5.05 kg, mean muscle mass is 37.49±4.50 kg, mean fat free mass is 39.80±4.70, mean BMD is 0.828±0.148 (g/㎠). In the result of linear regression analysis, age, height, weight, muscle mass, fat free mass, fat mass, BMI are significant determinants of BMD. In stepwise multiple regression analysis, age is the most significant determinant of BMD and besides age, fat mass is the most significant determinant of BMD among body composition. Conclusion: In postmenopausal women, age, height, weight, BMI, muscle mass, fat free mass, fat mass are significant determinants of BMD and besides age, fat free mass is the most significant determinant of BMD among the body composition. So, diet and exercise that increase fat free mass will contribute to bone density increment.