IL-10 Deficiency Aggravates Renal Inflammation, Fibrosis and Functional Failure in High-Fat Dieted Obese Mice

Kim Dae Hwan,Chun So Young,이은혜,Kim Bomi,Yoon BoHyun,Gil Haejung,Han Man-Hoon,Ha Yun-Sok,Lee Jun Nyung,Kwon Tae Gyun,김범수,장병익 한국조직공학과 재생의학회 2021 조직공학과 재생의학 Vol.18 No.3

BACKGROUND: High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. METHODS: To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High‐fat dieted C57BL/6 mice and (4) High‐fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. RESULTS: At week 12, high‐fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro‐inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. CONCLUSION: IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure. BACKGROUND: High-fat diet-induced obesity is one of the major cause of chronic renal failure. This obesity-related renal failure is mainly caused by inflammatory processes. However, the role of the major anti-inflammatory cytokine interleukin (IL)-10 has not been researched intensively. METHODS: To evaluate the effect of IL-10 deficiency on obesity-related renal failure, the in vivo study was carried with four animal groups; (1) Low-fat dieted C57BL/6 mice, (2) Low-fat dieted IL-10 knockout (KO) mice, (3) High‐fat dieted C57BL/6 mice and (4) High‐fat dieted IL-10 KO mice group. The analysis was carried with blood/urine chemistry, H&E, Oil-Red-O, periodic acid-Schiff and Masson’s trichrome staining immunohistochemistry and real-time PCR methods. RESULTS: At week 12, high‐fat dieted IL-10 KO mice showed 1) severe lipid accumulation in kidneys, cholesterol elevation (in total, serum kidney) and low-density lipoprotein increasion through the SCAP-SREBP2-LDLr pathway; (2) serious histopathologic alterations showing glomerulosclerosis, tubulointerstitial fibrosis and immune cell infiltration; (3) increased pro‐inflammatory cytokines and chemokines expression; (4) enhanced renal fibrosis; and (5) serious functional failure with high serum creatinine and BUN and proteinuria excretion compared to other groups. CONCLUSION: IL-10 deficiency aggravates renal inflammation, fibrosis and functional failure in high-fat dieted obese mice, thus IL-10 therapy could be applied to obesity-related chronic renal failure.

한국인 전반적 급진성 치주염 환자에서 IL-10 promoter 유전자 다변성에 관한 연구

류지선,김옥수,Ryn, Ji-Sun,Kim, Ok-Su 대한치주과학회 2007 Journal of Periodontal & Implant Science Vol.37 No.3

Genetic polymorphisms associated with aggressive periodontitis have previously been reported. Interleukin-10 is an immunoregulatory cytokine that plays a role in the pathogenesis of periodontitis. Individual capacity for IL-10 production appears to be under genetic influence, The aim of present investigation was to explore possible genetic association of IL-10 gene promoter polymorphisms with generalized aggressive periodontitis. The study population consisted of 37 generalized aggressive periodontitis patients from the Department of Periodontology, Chonnam National University Hospital and 27 control subjects, all the subjects were non-smokers, Genomic DNA was obtained from buccal swab. The IL-10promoter -597, -824, -1082 positions were genotyped by amplifying the polymorphic regions using polymerase chain reaction (PCR) , followed by restriction enzyme digestion and gel electrophoresis. IL-10-597 C (allele 1) to A (allele 2) and IL-10-824 C (allele 1) to T (allele 2) and IL-10-1082 G (allele 1) to A (allele 2) polymorphisms were examined. The results were as follows. 1. In patients, the distribution of genotypes C/C, C/A and NA at Il-10-597 was determined to be 13.5%, 37.8% and 48.7%, respectively and the distribution of genotypes at IL-10-824 was the same as that of IL-10-597. The distribution of genotypes G/G, G/A and NA at IL-10-1082 was found to be 2.7%, 16.2% and 81. 4%, respectively. No statistical difference in genotype distribution was found between the patient and control groups. 2. Allele 2 carriage rate at the three position of the IL-10 promoter region was higher in the control group than the patient group. 3. Allele 2 frequencies at IL-10-597 and -824 positions were higher in female group than male group and its difference was statistically significant(p<0.05). No significant difference in genotype distribution between the control and patient groups. Allele frequency between control and patient groups was not significantly different although allele 2 frequency at the three positions in the IL-10 promoter region appeared to be higher in control group. In conclusion, no clear association between IL-10 gene promoter polymorphisms and generalized aggressive periodontitis in Korean was observed.

천식유발 마우스에서의 폐 내 세포조성 변화와 IL-4 및 IL-10의 발현 양상

이수진,박세종,리천주,장양호,최농훈,Lee, Soo-Jin,Park, Se-Jong,Li, Tian-Zhu,Jang, Yang-Ho,Choe, Nong-Hoon 한국생명과학회 2006 생명과학회지 Vol.16 No.5

본 연구진은 일차로 BALB/C 마우스를 이용하여 항원으로 ovalbumin을 사용하여 천식을 유발하여 폐 내 세포구성에 미치는 영향을 다른 실험방법에 의해 만들어진 천식모델과 비교하여 살펴보았고 이차로 천식 발생에 중요한 역할을 하는 것으로 알려진 IL-4와 IL-10 knock out (KO) 마우스를 이용하여 천식모델을 구축하여 천식인자를 가진 개체에서의 반응과 천식관련인자가 결핍된 개체에서의 반응성의 차이를 살펴보았다. 천식의 유발은 실험 1일째 $20\;{\mu}g$ ovalbumin으로 감작시킨 후 실험 14일에 재감작을 시켰다. 그 후 nebulizer를 이용하여 nasal inhalation을 28일, 29일, 30일에 실시하여 천식을 유발시켰다. 천식 유발의 확인은 기관지폐포 세척술로 채취한 폐 내 세포액을 이용하여 총 세포수 및 염증세포의 증가와 폐 내 세포와 폐조직의 염색을 통해 분포율을 확인하였다. 천식의 발병 과정에서 IgE 관련 과민반응을 주도하는 IL-4와 Th2 세포의 기능을 억제한다고 알려진 IL-10의 면역화학염색을 통해 그 발현정도를 관찰하였다. BALB/c 마우스의 천식유발군의 경우 천식의 특징인 염증세포의 증가와 호산구의 증가와 세기관지 주위 염증세포의 침윤 및 기도 상피의 비후를 관찰할 수 있었다. 따라서 본 실험에 응용된 천식유발 방법은 적합하였으며 천식유발 절차가 성공적으로 수행되었음을 확인하였다. IL-4 및 IL-10 KO 마우스를 이용한 천식유발군의 경우 BALB/c 마우스를 이용한 천식유발군보다 호산구의 증가 정도가 미약하게 관찰되었고, 폐조직 내 염증세포의 침윤 정도도 감소하였다. 천식매개인자인 IL-4와 IL-10의 면역조직화학염색 결과에서도 양성반응이 거의 나타나지 않았다. 본 연구 결과, IL-10이 IL-4와 같이 천식과 관련하여 세기관지 염증 반응을 증가시키는 역할을 하는 것으로 생각된다. Asthma is a chronic inflammatory disorder of the airways, which characterized by bronchial hyperresponsiveness, reversible airflow limitation and respiratory symptoms. Internationally, the prevalence of asthma has been increased over last 3 decades. Recently, several studies of asthma have been reported with gradually increasing importance. To tesify the hypothesis that interleukin (IL)-4 and IL-10 may be an important determinant of the severity of airway inflammation, their expression was studied in mouse model of asthma. BALB/c mouse, IL-4 Knockout (KO) mouse and IL-10 KO mouse were sensitized with intraperitoneal injection of ovalbumin adsorbed to aluminum potassium sulfate, followed by challenges with intranasal ovalbumin on 3 consecutive days. The severity of pulmonary inflammation was assessed by eosinophilia in BAL fluid, number of total BAL cells, histopathological changes in lung tissues, and immunohistochemical staining against IL-4 and IL-10. In BAL fluid, the number of total cells was significantly increased in asthma induced mouse compare to the control. In asthma induced mouse, eosinophil was increased to 56% and neutrophil was 0.2%. In H &E stains, eosinophilic infiltration and epithelium hyperplasia were clearly noticed in asthma induced mouse. In immunohistochemical staining for IL-4 and IL-10, there was no positive reaction in control group. However, very strong reactions were appeared in asthma induced group. In this research, IL-4 and IL-10, which seem to play a central role in allergic asthma, KO mouse was utilized to test the causative relationship between airway inflammation and role of specific cytokine. Asthma induced IL-4 and IL-10 KO mice showed much decreased inflammatory reactions in the number of total BAL cells, in eosinophilic infiltration, and in immunohistochemical stains against diverse inflammatory proteins. These results suggest that IL-4 and IL-10 increase the asthmatic reactions in vivo mice model.

IL-15-Induced IL-10 Increases the Cytolytic Activity of Human Natural Killer Cells

Ju Yeong Park,이석형,윤석란,Young-Jun Park,정해용,김태돈,최인표 한국분자세포생물학회 2011 Molecules and cells Vol.32 No.3

Interleukin 10 (IL-10) is a multifunctional cytokine that regulates diverse functions of immune cells. Natural killer (NK) cells express the IL-10 and IL-10 receptor, but little is known about the function of IL-10 on NK cell activation. In this study, we show the expression and role of IL-10 in human NK cells. Among the cytokines tested, IL-15 was the most potent inducer of IL-10, with a maximal peak expression at 5 h after treatment. Furthermore, IL-10 receptor was shown to be expressed in NK cells. IL-10 alone had a significant effect on NK cytotoxicity which additively increased NK cell cytotoxicity in the presence of IL-15. Neutralizing IL-10 with anti-IL-10 antibody suppressed the inductive effect of IL-10 on NK cell cytotoxicity; however, IL-10 had no effect on IFN-γ or TNF-α production or NK cell activatory receptor expression. STAT signals are implicated as a key mediator of IL-10/IL-15 cytotoxicity response. Thus, the effect of IL-10 on NK cells is particularly interesting with regard to the STAT3 signal that was enhanced by IL-10 or IL-15.

Retrovirus 에 의해 IL-10 이 전이된 알레르겐 특이 CD4+ T Helper 림프구가 기도의 과민반응과 염증반응에 미치는 억제 효과

(Rosemarie . H . Dekruyff),(Dale . T . Umetsu),오재원(Jae Won Oh) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 2000 소아알레르기 및 호흡기학회지 Vol.10 No.4

목 적 : 기도 과민반웅과 염중반웅은 천식의 가장 기본적 특징 중 하나이며, 이 반응들은 여러 관련 세포들에 의한 염증 반응의 정도에 의존한다. 특히 알레르기반응에 있어서 Th2 림프구에서 생산되는 cytokines의 역할이 Th1 림프구 보다 더욱 중요한 것으로 알려져 있다. IL-10은 T, B림프구, 단핵세포 등에서 생성되며 비만세포의 cytokines 생성과 IgE 생성을 억제하며, 기도나 복막부위에서 T 림프구와 호산구의 축적과 활동을 억제하는 등 항알레르기, 항염증반응의 역할을 하는 것으로 알려져 있다. 본 연구에서는 retrovirus를 이용하여 IL-10을 CD4+ Th 림프구에 전이하여 이 세포를 중증면역결핍백서에 정맥 주입한 후 알레르겐 특이 Th2 림프구에 의해 유발된 기도 과민반응과 염증반응을 억제할 수 있는지를 밝히고자 하였다. 방 법 : IL-10 유전자를 plasmid에 붙인 retrovirus을 이용하여 IL-10이 전이된 CD4+ Th 림프구를 중증면역결핍(SCID) 백서나 정상 Balb/c 백서에 정맥 주입한 후 Th2 림프구에 의한 기도 과민반응의 변화를 메타콜린 자극에 따른 전신 체적변동기록법을 이용하여 측정하였으며, 이 억제 효과가 항 IL-10 단일클론항체를 투여하여 소멸되는지를 관찰하였다. 결 과 : 유전자 조작에 의해 IL-10이 전이된 CD4+ T세포가 OVA 특이 Th2 세포에 의한 기도 과민반응을 억제하였으며, 이러한 IL-10의 억제 효과는 항 IL-10 단일클론항체를 투여하였을 때 다시 기도 과민반응이 소멸되었다. 결 론 : IL-10이 전이된 CD4+ T세포는 항원에 특이하게 Th2 세포의 기능을 억제할 뿐 아니라 항원 특이 Th2 세포에 의한 기도 과민반응의 유발을 억제할 수 있음을 시사하고 있다. Purpose : Asthma is characterized by airway hyperreactivity to a variety of specific and nonspecific stimuli, by chronic airway inflammation with pulmonary eosinophilia, by mucus hypersecretion, and by increased serum IgE levels. T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanism that inhibit Th2 cell function in vivo are not well understood. Methods : Using gene therapy, Th-cell lines were transferred intravenously into histocompatible SCII) or OVA immunized Balb/c mice. Airway responsiveness was assessed by methacholine-induced airflow obstruction from conscious mice placed in a whole-body plethysmograph. Pulmonary airflow obstruction was measured by enhanced pause(Penh). Results : We demonstrated that ovalbumin-specific(OVA-specific) Th cells engineered to express IL-10 abolished airway hyperreactivity induced by OVA-specific Th2 effector cells in SCID and Balb/c mice. The inhibitory effect of IL-10 transduced Th cells was antigen-specific and was reversed by neutralization of IL-10. Conclusion : Our results demonstrate that IL-10 transduced CD4+ Th cells in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity.

결핵성 흉수에서 IL-10, IL-12, IFN-$\gamma$, ADA 측정의 의의

전두수,윤상명,박삼석,이효진,김윤성,이민기,박순규,Jeon, Doo-Soo,Yun, Sang-Myung,Park, Sam-Seok,Lee, Hyo-Jin,Kim, Yun-Seong,Lee, Min-Ki,Park, Soon-Kew 대한결핵및호흡기학회 1998 Tuberculosis and Respiratory Diseases Vol.45 No.2

Background: Cell mediated immune response mediated by interaction between CD4+ T lymphocytes and macrophagies is thought to play an important role in tuberculous pleurisy. This interaction is dependent on the interplay of various cytokines. The immunologic response of tuberculous pleurisy is thought to depend on the balance between helper T cell(Th1) cytokine Interleukin-12, Interferon gamma and Th2 cytokine IL-4, IL-10. To understand immunologic mechanism in tuberculous pleurisy and evaluate diagnostic value of these cytokines, the concentrations of Th1 cytokine IL-12, IFN -$\gamma$ and Th2 cytokine IL-10 were measured in tuberculous pleurisy and malignant pleural effusion group. Material and Methods: The concentrations of IL-10, IL-12 and IFN-$\gamma$ were measured by ELISA method in pleural fluids and serums of 20 patients with tuberculous pleurisy and 20 patients with malignant pleural effusion ADA activities were measured by spetrophotomery in pleural fluids of both groups. Results: In tuberculous pleurisy, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $121.3{\pm}83.7$ pg/mL, $571.4{\pm}472.7$ pg/mL and $420.4{\pm}285.9$ pg/mL. These were significantly higher than that of serum, $21.2{\pm}60.9$ pg/mL, 194.5 pg/mL, $30.1{\pm}18.3$ pg/mL respectively(p< 0.01). In malignant pleural effusion, the mean concentrations of IL-10, IL-12 and IFN-$\gamma$ of pleural fluids showed $88.4{\pm}40.4$ pg/mL, $306.5{\pm}271.1$ pg/mL and $30.5{\pm}54.8$ pg/mL respectively. Compared with that of serum ($43.4{\pm}67.2$ pg/mL, $206.8{\pm}160.6$ pg/mL, $14.6{\pm}3.3$ pg/mL), only IL-10 was significantly higher (p<0.001), but IL-12, IFN-$\gamma$ were not significant. In tuberculous pleural effusion compared with malignant pleural effusion, the concentration of IL-12, IFN-$\gamma$, ADA were significantly higher (p=value 0.046, <0.001, <0.001), but IL-10 was not significant. For differential diagnosis of tuberculous pleurisy from malignant pleural effusion, using cut-off value of IL-12, IFN-$\gamma$, ADA as 300 pg/mL. 100 pg/mL, 45 U/L, the sensitivity/specificity were 60%/70%, 90%/87.5%, 85%/90% respectively. Conclusion: In tuberculous pleurisy, IL-10, IL-12 and IFN-$\gamma$ were selectively concentrated highly in pleural space than serum. Compared with malignant pleural effusion, IL-12 and IFN-$\gamma$ were significantly higher, but IL-10 were not in tuberculous pleural effusion. The results suggest that Th1 pathway contributes to immune resistant mechanism in tuberculous pleurisy. IFN-$\gamma$ and ADA revealed useful methods of differential diagnosis in tuberculous pleurisy from malignant pleural effusion. 연구배경: 결핵성 흉막염은 면학적으로 흉강내에 국소적으로 활성화된 CD4+ T림프구와 대식세포가 관여하는 세포매개면역이 중요한 역할을 하며 이들의 상호작용은 다양한 사이토카인에 의해 좌우된다고 알려져 있다. 특히 helper T cell type 1 (Th1) 사이토카인인 IL-12 및 IFN-$\gamma$와 Th2 사이토카인인 IL-4 및 IL-10간의 균형이 세포매개반응의 정도를 결정한다고 생각되고 있다. 본 연구는 세포매개면역반응의 지표로서 Th1 사이토카인인 IL-12, IFN-$\gamma$와 이들과 길항적으로 작용한다고 알려져있는 Th2 사이토카인 중 IL-10이 결핵성 흉수내에 어떻게 표현되는지를 검사하여 대조군인 악성 흉수와 비교함으로써 결핵성 흉막염의 변역학적 기전을 이해하는데 도움이 되고자 하였으며 아울러 사이토카인의 진단적 유용성을 알아보고자 하였다. 방 법: 각 20명의 결핵성 흉막염과 악성 흉막염 환자를 대상으로 흉수와 혈장에서 IL-10, IL-12, IFN-$\gamma$를 측정하고 흉수에서의 ADA를 측정하여 비교하였다. 사이토카인은 대상환자의 혈액과 흉수를 원심분리하여 얻은 상층액을 ELISA 방법으로 측정하였고 ADA 활성도는 비색법으로 측정하였다. 결 과: 결핵성 흉막염 환자에서 흉수의 IL-10, IL-12, IFN-$\gamma$의 농도는 $121.3{\pm}83.7$ pg/mL, $571.4{\pm}472.7$ pg/mL, $420.4{\pm}285.9$ pg/mL로 혈장의 $21.2{\pm}60.9$ pg/mL, $194.5{\pm}67.6$ pg/mL, $30.1{\pm}18.3$ pg/mL 보다 모두 유의하게 높았다 (p<0.01). 악성 흉막염 환자에서 흉수의 IL-10, IL-12, IFN-$\gamma$의 농도는 $88.4{\pm}40.4$ pg/mL, $306.5{\pm}271.1$ pg/mL, $30.5{\pm}54.8$ pg/mL로 혈장의 $43.4 {\pm}67.2$ pg/mL, $206.8{\pm}160.6$ pg/mL, $14.6{\pm}3.3$ pg/mL와 비교하였을때 IL-10 만이 유의하게 높았고 (p<0.001) IL12, IFN-$\gamma$에선 유의한 차이가 없었다. 결핵성 흉막염과 악성 흉막염 환자의 흉수에서의 농도를 비교하였을 때 IL-12, IFN-$\gamma$, ADA는 결핵성 흉막염에서 유의하게 높았으나 (p=0.046, <0.001, <0.001) IL-10은 유의한 차이가 없었다. 결핵성 흉수염을 악성 흉수염과 감별하는데 있어 IL-12, IFN-$\gamma$, ADA의 기준을 각각 300 pg/mL, 100 pg/mL, 45 U/L으로 하였을때 민감도/특이도는 IL-12에서 60%/70%, IFN-$\gamma$에서 90%/85%, ADA 에서 85%/90%였다. 결 론: 결핵성 흉수에서 흉강내에 Th1 사이토카인인 IL-12, IFN-$\gamma$와 함께 IL-10이 증가되어 있었고 악성흉수와 비교했을때 IL-12, IFN-$\gamma$는 유의하게 증가되어 있었으나 IL-10은 의의가 없었다. 따라서 결핵성 흉막염의 면역기전에 Th1 경로의 세포매개변역반응이 주로 관여함을 확인할 수 있었고 국소적인 IL-10 증가의 임상적 의의는 추후의 연구가 필요할 것으로 생각된다. 또한 IFN-$\gamma$와 ADA는 결핵성 흉수와 악성 흉수와의 감별에 유용한 진단법으로 생각된다.

정신분열병에서 Interleukin-10 유전자의 제한효소절편길이 다형성

전태연,배치운 대한신경정신의학회 2000 신경정신의학 Vol.39 No.6

연구목적 : 중추신경계와 면역기능의 조절에 관여하는 싸이토카인 중 Interleukin-10 유전자다형성을 분석하여 정신분열병과의 면역·유전학적 관련성을 알아보고자 하였다. 방 법 : DSM-IV에 의거하여 정신분열병으로 진단된 환자 114명을 선정하였으며 가톨릭조혈모세포정보은행에서 보유하고 있는 정상한국인 146명의 자료를 대조군으로 이용하였다. 전혈에서 DSP(direct sample preparation) 방법으로 DNA를 추출한 후 중합효소 연쇄반응(polymerase chain reaction)을 이용하여 IL-10유전자 부위를 증폭하였다. 이들 중폭산물을 제한 효소(MaeⅢ)로 분절 후 IL10*C와 IL10*T의 2가지 대립유전자에 대한 제한효소절편길이다형성을 조사하였다. 결 과 : 1) 정신분열병 군과 정상 대조군 간에 IL-10유전자형 IL-10*T/T, IL-10*T/C및 IL-10*C/C의 발현 빈도에서 유의한 차이가 없었다 (각 46.8%대 48.6%,44% 대 42.5%, 9.2% 대 8.9%). 2) 두 군간 IL-10*T와 IL-10*C 유전자 발현 빈도에는 유의한 차이가 없었다.(각 68.8%대 69.9%, 31.2% 대 30.1%). 결 론 : IL-10 유전자형 및 대립유전자의 발현빈도는 정신분열병 환자군과 정상 대조군 사이에 차이가 없었다. 향후 연구에서는 다양한 임상적 변인 등을 포함한 통합적인 조사가 이루어져야 하겠다. Objective : Recently, molecular genetic methods have been progressed, this study was to investigate the relationship between schizophrenia and immunologic aspects by analyzing polymorphism of IL-10 gene, which is involved in interaction of immunologic system and CNS. Method : 141 schizophrenic patients diagnosed by DSM-IV were included and data of 146 normal controls obtained from the Catholic Hemopoietic Stem Cell Information Bank of Korea were used in this study. DNA was extracted from whole blood, thereafter amplified by polymerase chain reaction, and digested by MaeⅢ After that procedure, we obtained and assessed RFLP of two alleles, IL-10T and IL-10C. All data were analyzed by x² test with two-tailed Fisher's exact test. Results : 1) There were no significant differences genotype frequencies of IL-10*T/T, IL-10*T/C, and IL-10*C/C in between schizophrenic patients group and control group. 2) There were no significant differences gene frequencies of IL-10*T and IL-10*C in between schizophrenic patients group and control group. Conclusion : We did not verified the frequency differences of IL-10*T/*IL-10*C gene between schizophrenic patients and normal controls, respectively. We do suggest that further systematic studies including various clinical variables should be conducted.

rIL-10 enhances IL-10 signalling proteins in foetal alveolar type II cells exposed to hyperoxia

Lee, Hyeon-Soo,Lee, Dong Gun John WileySons, Ltd 2015 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.19 No.7

<P>Although the mechanisms by which hyperoxia promotes bronchopulmonary dysplasia are not fully defined, the inability to maintain optimal interleukin (IL)-10 levels in response to injury secondary to hyperoxia seems to play an important role. We previously defined that hyperoxia decreased IL-10 production and pre-treatment with recombinant IL-10 (rIL-10) protected these cells from injury. The objectives of these studies were to investigate the responses of IL-10 receptors (IL-10Rs) and IL-10 signalling proteins (IL-10SPs) in hyperoxic foetal alveolar type II cells (FATIICs) with and without rIL-10. FATIICs were isolated on embryonic day 19 and exposed to 65%-oxygen for 24 hrs. Cells in room air were used as controls. IL-10Rs protein and mRNA were analysed by ELISA and qRT-PCR, respectively. IL-10SPs were assessed by Western blot using phospho-specific antibodies. IL-10Rs protein and mRNA increased significantly in FATIICs during hyperoxia, but JAK1 and TYK2 phosphorylation showed the opposite pattern. To evaluate the impact of IL-8 (shown previously to be increased) and the role of IL-10Rs, IL-10SPs were reanalysed in IL-8-added normoxic cells and in the IL-10Rs’ siRNA-treated hyperoxic cells. The IL-10Rs’ siRNA-treated hyperoxic cells and IL-8-added normoxic cells showed the same pattern in IL10SPs with the hyproxic cells. And pre-treatment with rIL-10 prior to hyperoxia exposure increased phosphorylated IL-10SPs, compared to the rIL-10-untreated hyperoxic cells. These studies suggest that JAK1 and TYK2 were significantly suppressed during hyperoxia, where IL-8 may play a role, and rIL-10 may have an effect on reverting the suppressed JAK1 and TYK2 in FATIICs exposed to hyperoxia.</P>

자궁내막증 환자에서 복강내의 IL-6와 IL-10의 변화양상에 관한 연구

이경석(Kyung Suk Lee),강정배(Jeong Bae Kang),김홍배(Hong Bae Kim),이근영(Keun Young Lee),강성원(Sung Won Kang) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.11

목적: 자궁내막증과 이로 인한 불임의 원인으로 여겨지고 있는 면역학적 인자 중 세포 매개성 면역계의 변화양상을 규명하기 위하여 자궁내막증 환자와 정상인의 복강액을 채취하여 면역세포의 분포양상을 비교분석하고자 IL-6와 IL-10을 측정하였다. 연구방법: 1997년 10월부터 1998년 10월까지 한림대학교 산부인과를 방문하여 불임검사, 불임시술 또는 양성 골반 질환의 진단 및 치료를 목적으로 복강경 또는 개복술을 시행한 여성 57명을 대상으로 이들 중 육안적 또는 조직검사로 자궁내막증으로 확진된 29명을 연구군으로 나머지 자궁내막증의 증상과 소견이 없는 28명을 대조군으로 하였다. 두군의 복강액에서 IL-6와 IL-10을 ELISA 방법으로 측정하였다. 결과: 복강액의 IL-6의 농도는 자궁내막증군에서는 1320.3121pg/ml로 대조군의 1017113 pg/ml보다 유의하게 증가하였고 (p=0.03) IL-10의 농도도 자궁내막증군에서 1.090.04 pg/ml로 대조군의 2.190.03 pg/ml보다 유의하게 감소하였다 (p=0.03). 자궁내막증 여성의 생리주기별 농도변화는 IL-6는 증식기보다 분비기에 유의하게 증가한 반면 (p=0.02) IL-10은 차이가 없었다. 자궁내막증군 중에서도 IL-6는 가임여성보다 불임여성에서 유의하게 증가하였고 (p=0.03) IL-10은 두 군 간에 유의한 차이는 없었다. 자궁내막증의 병기에 따른 IL-6와 IL-10의 농도를 각각 비교한 결과 통계학적으로 유의한 변화는 없었다. 결론: 자궁내막증 환자의 복강액에서 세포매개성 면역변화로 IL-6가 증가하고 IL-10은 감소하며 이러한 사이토카인의 변화가 자궁내막증의 생성과 진행, 증상발현에 관여하며 기계적폐쇄로 인한 배란장애와 난소이동의 장애, 수정력 감소, 착상장애로 불임이 유발되는 것으로 생각되며 이들 면역계통의 변화에 대한 더 많은 연구가 필요하리라 여겨진다. Objective: Endometriosis is a disease affecting a large population of women all over the world. A local sterile inflammation occurs in the peritonel cavity of patients with endometriosis. It suggests that immunological events play a major role in the pathogenesis of endometriosis. We have studied the levels of serveral T cell and monocyte derived cytokines, especially IL-6 (promoter of immune response) and IL-10 (inhibitor of immune response), in the peritoneal fluid of patients with endometriosis to characterize the change of immune response that occurs at the site of endometriosis. Method: This study was performed in Hallym university hospital from October, 1997 to October 1998 and enrolled 29 women with gross or microscopic findings of minimal to severe endometriosis in case group, and 28 women without visual evidence of pelvic endometriosis and with benign gynecologic disease in control group. IL-6 and IL-10 levels in the peritoneal fluid were determined using commercial ELISA and compared between endometriosis and controls and between fertile and infertile women with endometriosis and according to the revised American Fertility Society classification. Result: IL-6 was higher and IL-10 was lower in the peritoneal fluid of endometriosis group than of control group. Cyclic variations in the IL-6 concentrations were seen in endometriosis group : the concentrations in the secretory phase were significantly higher than those in the proliferative phase. In endometriosis group, IL-6 concentrations of infertile women were higher than fertile women. Both IL-6 and IL-10 in the peritoneal fluid of endomtriosis group did not show significant correlation according to r-AFS stages. Conclusion: Increased IL-6 and decreased IL-10 levels in the peritoneal fluid may be related to infertility and pathogenesis in the endometriosis, suggesting that partially contribute to the disturbed immune regulation observed in endometriosis.

아토피 피부염에서 혈중 Interferon-γ , Interleukin-4 , Interleukin - 5 및 Interleukin - 10의 농도

이기영(Ki Young Lee),노건웅(Geun Woong Noh) 대한소아알레르기호흡기학회(구 대한소아알레르기 및 호흡기학회) 1998 소아알레르기 및 호흡기학회지 Vol.8 No.1

목 적 : 아토피 피부염은 알레르기 기전에 의한 만성 질환으로 interferon(IFN)-γ의 생성능이 감소하여 있고, interleukin(IL)-4의 생성능이 증가하여 있다. IFN-γ와 IL-4로 대변되는 Th1/Th2 세포의 불균형으로 인하여 IgE 생성이 증가하는 것으로 알려져 있는데, IgE의 증가는 아토피 피부염의 주요한 문제점으로 알려져 있다. 아토피 피부염에서 cytokine의 생성능에 관한 연구가 많지만, 실제 혈중농도에 관하여는 아직 확실하게 보고되어 있지 않다. 본 연구의 목적은 아토피 피부염에 관여하는 것으로 알려진 IFN-γ, IL-4 및 IL-5와 Th2 세포에서 생성되는 것으로 잘 알려져 있는 IL-10의 혈중 농도가 아토피 피부염에서 임상적으로 정상에 비하여 의의있는 변화를 나타내는지를 알아보기 위하여 본 연구를 시행하였다. IgE의 생성에 관여하는 것으로 알려진 IFN-γ와 IL-4의 농도가 혈중 IgE 농도와 상관관계가 있는지 살펴보았다. 대상 및 대상 : 아토피 피부염 환자군은 Hanifin과 Rajka의 기준을 만족시키는 아토피 피부염 환자 105명과 정상인 40명을 대조군으로 하였다. 대상자로부터 정맥혈 10ml을 채취하고 일반 혈액검사, 총 호산구수 및 혈중 IgE치를 측정하였다. 검체들에서 혈장을 분리하고 ELSIA법을 이용하여 IFN-γ, IL-4, IL-5 및 IL-10의 농도를 측정하여 정상 대조군과 비교하였다. 결 과 : 백혈구에서 호산구의 비 및 총 호산구의 수, 그리고 혈중 IgE 치 모두 아토피 피부염 환자군에서 의미있게 증가하였으나, 혈중 백혈구의 수에는 두군에서 차이가 없었다. IFN-γ의 혈중 농도는 아토피 피부염 환자군의 경우에 0.58±2.12pg/ml, 정상 대조군 5.20±2.60pg/ml으로 아토피 피부염에서 의미있게 낮았다(P<0.01). IL-4의 혈중 농도는 아토피 피부염 환자군에서 1.00±2.05pg/ml이었으나, 정상 대조군에서는 검출되지 않았고 (P<0.001), IL-5의 혈중 농도는 아토피 피부염에서 2.18±1.96pg/ml이었으나, 정상 대조군에서는 검출되지 않았다(P<0.001), IL-10의 혈중 농도는 아토피 피부염에서 2.36±3.38pg/ml, 정상 대조군에서는 9.78±4.52pg/ml로 아토피 피부염에서 정상 대조군에 비하여 오히려 낮은 결과를 보였다(P<0.01). 혈중 IgE치와 IFN-γ 및 IL씨의 혈중 농도간에는 유의한 상관관계를 보이지 않았다. 결 론 : 아토피 피부염에서 IFN-γ 및 IL-10의 혈중 농도는 정상보다 낮고, IL-4 및 IL-5 혈중 농도는 높다. 아토피 피부염에서 IFN-γ, IL-4, IL-5 및 IL-10의 혈중농도는 임상적으로 의미가 있다. 혈중 IFN-γ 및 IL-4 농도는 혈중 IgE치와 유의한 상관관계를 보이지 않았다. Purpose: There is reduced IFN-γ production with increased IL-4 production in atopic dermatitis. IgE production is known to increase from an imbalance of IFN-γ and IL-4 production. IgE overproduction is regarded as a major problem in the pathogenesis of atopic dermatitis. In this study we evaluated the significances of plasma IFN-γ, IL-4, IL-5 and IL-10 concentrations in atopic dermatitis. Also the correlation between IL-4 and IgE levels as well as IFN-γ and IgE levels were tested. Methods : One hundred and five(105) atopic dermatitis patients who fulfilled the criteria of Hanifin and Rajka were tested as an atopic dermatitis patient group. Forty(40) normal controls who have not had any personal or family history of allergic diseases were tested as a normal control group. Routine hematologic tests, plasma IgE levels and total eosinophil counts were tested in both groups. Also plasma IFN-γ, IL-4, IL-5 and IL-10 concentrations were measured using high-sensitive IL-4, IL-5, IL-10 and IFN-γ ELISA kits in both groups. Results : There was no noticeable difference in WBC counts between the atopic dermatitis group and the normal control group. In comparison, eosinophil percents in WBC and total eosinophil counts were significantly high in the atopic dermatitis group. Plasma IgE levels were also markedly elevated in the atopic dermatitis group. Plasm IFN-γ levels were significantly low in the atopic dermatitis group(0.58±2.12 pg/ml) as compared with normal control group(5.20±2.60pg/ml)(P<0.01). IL-4 and IL-5 were not detected in normal controls. But in the atopic dermatitis group plasma IL-4 concentration was 1.00±2.05pg/ml and IL-5 was 2.18±1.96pg/ml. Plasma IL-10 concentration was significantly low in the atopic dermatitis group(2.36±3.38 pg/ml) as compared with the normal control group(9.78±4.52pg/ml)(P<0.01). Conclusions : Plasma IFN-γ, IL-4, IL-5 and IL-10 levels were clinically significant in atopic dermatitis. However, plasma IL-10 levels of the atopic dermatitis was lower as compared to that of the normal subject. There was no significant correlation among plasma IFN-γ, IL-4 levels, and blood IgE levels.