폐포 대식세포 및 단핵구가 Interleukin-2 Enhanced Natural Killer 및 LAK Activity에 미치는 영향

조철호 ( Jo Cheol Ho ),김병일 ( Kim Byeong Il ),김세규 ( Kim Se Gyu ),천선희 ( Cheon Seon Hui ),김형중 ( Kim Hyeong Jung ),장준 ( Jang Jun ),안철민 ( An Cheol Min ),김성규 ( Kim Seong Gyu ),이원영 ( Lee Won Yeong ),윤정구 ( Yun J 대한내과학회 1992 대한내과학회지 Vol.42 No.5

저자들은 폐포 대식세포 및 말초혈액내의 단핵구가 NK 활성도 및 LAK 활성도에 미치는 영향을 보기위하여, 임파구에 여러 가지 농도(0, 100 : 1, 10 : 1, 1 : 1)의 폐포 대식세포와 단핵구를 넣어 IL-2 enhanced NK 활성도 및 LAK 활성도를 비교하여 다음과 같은 결과를 얻었다. 1) 여러 가지 농도의 단해구는 IL-2 enchanced NK 활성도 및 LAK 활성도에 영향을 미치지 않았다. 2) 동량의 페포대식세포(임파구 : 폐포 대식세포= 1 : 1)는 IL-2 enhanced NK 활성도를 의의있게 억제하였으나(p<0.05), 소량의 폐포대식세포(임파구 : 폐포 대식세포-10 : 1과 100 : 1)는 IL-2 enhanced NK 활성도를 억제하지 못하였다. 3) 임팍와 폐포 대식세포의 비율이 1 : 1과 10 : 1에서는 LAK 활성도를 의의있게 억제하였으나, 소량의 폐포대식세포(임파구 : 폐포 대식세포=100 : 1)는 LAK 활성도를 억제하지 못하였다(p<0.05). 이상의 결과로 IL-2 enhanced NK 활성도 및 LAK 활성도는 폐포 대식세포의 양에 비례하여 억제되었으나, 말초혈액내의 단핵구에 의해서는 영향받지 않는 것을 알 수 있었다. Alveolar macrophages (AM) are thought to function as primary effector cells against tumors growing in the lung. Systemic administration of lymphokine activated killer (LAK) cells and IL-2 resulted in partial antitumor response in patients with advanced cancer. LAK activity is influenced by various factors. We studied the effects of AM and blood monocytes from healthy donors on IL-2 enhanced NK activity against K-562 cells and LAK activity against Raji cells utilizing a 4h ^(51)Cr release assay. The following results were obtained: 1) The addition of different doses of human blood monocytes showed no suppression or enhancement of IL-2 enhanced NK and LAK activity. 2) The addition of high dose of AM (Lymphocyte: AM=1:1) significantly suppressed IL-2 enhanced NK activity. Smaller doses of AM (Lymphocyte: AM= 10:1and 100:1) did not suppress IL-2 enhanced NK activity. 3) The addition of high dose of AM (Lymphocyte: AM = 1:1 and 10:1) significantly suppressed LAK activity. The smallest dose of AM (Lymphocyte: AM= 100:1) did not suppress LAK activity. In conclusion, IL-2 enhanced NK and LAK activity were dose-dependently suppressed by human alveolar macrophages. However IL-2 enhanced NK and LAK activity were not suppressed by blood monocytes.

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>

PLZF⁺ Innate T Cells Support the TGF-β-Dependent Generation of Activated/Memory-Like Regulatory T Cells

Kang, Byung Hyun,Park, Hyo Jin,Park, Hi Jung,Lee, Jae-Il,Park, Seong Hoe,Jung, Kyeong Cheon Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.6

PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether $PLZF^+$ innate T cells also affect the development and function of $Foxp3^+$ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant $PLZF^+$ CD4 T cells and invariant natural killer T cells, respectively, revealed that $Foxp3^+$ T cells in these mice exhibited a $CD103^+$ activated/memorylike phenotype. The frequency of $CD103^+$ regulatory T cells was considerably decreased in $PLZF^+$ cell-deficient $CIITA^{Tg}Plzf^{lu/lu}$ and $BALB/c.CD1d^{-/-}$ mice as well as in an IL-4-deficient background, such as in $CIITA^{Tg}IL-4^{-/-}$ and $BALB/c.IL-4^{-/-}$ mice, indicating that the acquisition of an activated/ memory-like phenotype was dependent on $PLZF^+$ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF-${\beta}$ enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/ memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of $CIITA^{Tg}PIV^{-/-}$ mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that $PLZF^+$ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.

PLZF+ Innate T Cells Support the TGF-beta-Dependent Generation of Activated/Memory-Like Regulatory T Cells

Kyeong-Cheon Jung,Byung Hyun Kang,Hyo Jin Park,Hi Jung Park,Jae-il Lee,Seong Hoe Park 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.6

PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether PLZF+ innate T cells also affect the development and function of Foxp3+ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant PLZF+ CD4 T cells and invariant natural killer T cells, respectively, revealed that Foxp3+ T cells in these mice exhibited a CD103+ activated/memory-like phenotype. The frequency of CD103+ regulatory T cells was considerably decreased in PLZF+ cell-deficient CII-TATgPlzflu/lu and BALB/c.CD1d−/− mice as well as in an IL-4-deficient background, such as in CIITATgIL-4−/− and BALB/ c.IL-4−/− mice, indicating that the acquisition of an activated/memory-like phenotype was dependent on PLZF+ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF- enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of CIITATgPIV-/- mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that PLZF+ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.

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.

The association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression in patients with rheumatoid arthritis

Cheon, Yun-Hong,Lee, Seung-Geun,Kim, Mingyo,Kim, Hyun-Ok,Sun Suh, Young,Park, Ki-Soo,Kim, Rock Bum,Yang, Hyun-Su,Kim, Ji-Min,Son, Chang-Nam,Kyoung Park, Eun,Kim, Sang-Hyon,Lee, Sang-Il Elsevier 2018 Brain, behavior, and immunity Vol.73 No.-

<P><B>Abstract</B></P> <P>Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N = 474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22–4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01–2.53]) and severity of fatigue (OR 1.26 95% CI 1.15–1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one’s capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Prevalence of depression in patients with rheumatoid arthritis (RA) was analyzed. </LI> <LI> Risk factors for depression and deterioration of depressive symptoms and were analyzed. </LI> <LI> Depression was related with disease activity in RA. </LI> <LI> Depression in RA was associated with impaired ability to perform activities of daily life. </LI> <LI> Among neurotrophic factors, the level of BDNF was related with depression in RA patients. </LI> <LI> The level of pro-inflammatory cytokines were not related with depression in RA patients. </LI> </UL> </P>

Effect of IL-4 on the Development and Function of Memory-like CD8 T Cells in the Peripheral Lymphoid Tissues

Hi-Jung Park,Ara Lee,Jae-Il Lee,Seong Hoe Park,Sang-Jun Ha,Kyeong Cheon Jung 대한면역학회 2016 Immune Network Vol.16 No.2

들깨(Perilla frutescens) 새싹 추출물의 항산화 및 항염 효과

정승일(Seung-Il Jeong),김현수(Hyeon Soo Kim),전인화(In Hwa Jeon),강현주(Hyun Ju Kang),목지예(Ji Ye Mok),천춘진(Chun Jin Cheon),유현희(Hyeon Hee Yu),정선일(Seon Il Jang) 한국식품과학회 2014 한국식품과학회지 Vol.46 No.1

본 연구는 들깨 새싹 추출물의 항산화, 항염증 및 항부종에 대한 효과를 조사하였다. 들깨 새싹 추출물은 DPPH와 ABTS 라디칼을 효과적으로 제거하는 항산화 활성이 우수하였다. 또한 들깨 새싹 추출물은 활성화된 설치류 유래 대식세포주인 RAW 264.7세포와 인간 유래 HMC-1 세포의 TNF-α와 IL-1β를 효과적으로 억제하였다. 더욱이 마우스의 귀와 발 부종을 억제하는 우수한 효과가 있었다. 이러한 결과는 들깨 새싹 추출물은 항산화제로 사용될 수 있을 뿐만 아니라 항염증과 항부종에 효과적인 물질이라는 것을 제시해주었다. 이와 관련된 들깨 새싹 추출물의 기능성에 대해서는 앞으로 분자생화학적 수준에서 더 연구해야할 필요성이 있는 것으로 사료된다. We investigated the effects of an ethanol extract from Perilla frutescens sprouts (PFSE) as an antioxidant, and its effects on edema and inflammation in RAW 264.7 cells and HMC-1 cells. The antioxidant activities (DPPH and ABTS radical scavenging) of PFSE were similar to those of butylated hydroxytoluene (BHT) and (±)-6-hydroxy-2,5,7,8- tetramethylchromane-2-carboxylic acid (Trolox). We also investigated the anti-inflammatory effects of PFSE on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and HMC-1 cells stimulated with phorbol 12-myristate 13-acetate (PMA) with the calcium ionophore A23187. TNF-α and IL-1β production, which had been increased by treatment with LPS or PMA plus A23187, were significantly inhibited by PFSE in a dose-dependent manner. Furthermore, PFSE significantly reduced the xylene-induced ear edema and the carrageenan-induced paw edema of ICR mice in a dosedependent manner. The effects of PFSE (200 mg/kg) in reducing ear and paw edema were similar to those of aspirin (50mg/kg). These results suggest that PFSE can be potentially used as a medicine for treating oxidative stress, an edematous and inflammatory disease.

Genetic polymorphisms of IL-23R and IL-17A and novel insights into their associations with inflammatory bowel disease.

Kim, Seung Won,Kim, Eun Soo,Moon, Chang Mo,Park, Jae Jun,Kim, Tae Il,Kim, Won Ho,Cheon, Jae Hee British Medical Association 2011 Gut: journal of the British Society of Gastroenter Vol.60 No.11

<P>To identify the associations of genetic and epigenetic variations in IL-23R and IL-17A with inflammatory bowel diseases (IBD).</P>

위장관 ; Lipopolysaccharide로 유도된 HT-29 세포주의 염증에서 Lactobacillus rhamnosus GG의 항염증 작용과 기전

이상길 ( Sang Kil Lee ),양경민 ( Kyung Min Yang ),천재희 ( Jae Hee Cheon ),김태일 ( Tae Il Kim ),김원호 ( Won Ho Kim ) 대한소화기학회 2012 대한소화기학회지 Vol.60 No.2

Background/Aims: Probiotics are live non-pathogenic organisms that belong to the resident microflora, and confer health benefits by multiple mechanisms. Lactobacillus rhamnosus GG (LGG) is one of the probiotic bacteria that ameliorates intestinal injury and inflammation caused by various stimuli. We aimed to evaluate the anti-inflammatory effect and mechanism of LGG in lipopolysaccharide (LPS)-stimulated HT-29 cells. Methods: HT-29 cells were stimulated with interleukin (IL)-1β (2 ng/mL), tumor necrosis factor (TNF)-α (20 ng/mL), and LPS (20 μg/mL) in the presence or absence of LGG (107-109 colony forming units/mL). Production of the pro-inflammatory chemokine IL-8 was measured by ELISA and semi-quantitative PCR. Transcriptional activity of NF-κB-responsive gene was evaluated by luciferase assay with reporter gene. Toll-like receptor 4 (TLR4) mRNA expression was assessed by semi-quantitative PCR. The IκBα degradation was evaluated by western blot and intranuclear translocation of NF-κB was determined by western blot and immunofluorescence. Results: LGG did not affect the viability of HT-29 cells. Pretreatment of HT-29 cells with LGG significantly blocked TNF-α, and LPS induced IL-8 activation at both mRNA and protein level (p<0.05). Pretreatment of HT-29 cells with LGG attenuated LPS-induced NF-κB nuclear translocation and also blocked LPS-induced IκBα degradation. LGG also down-regulated TLR4 mRNA activated by LPS. Conclusions: LGG attenuates LPS induced inflammation, and this may be associated with TLR4/NF-κB down-regulation. (Korean J Gastroenterol 2012;60:86-93)