호산구의 활성 억제 사이토카인과 억제 기작의 규명

박춘식 ( Park Chun Sig ),최은남 ( Choe Eun Nam ),이영목 ( Lee Yeong Mog ),박성우 ( Park Seong U ),장안수 ( Jang An Su ),이준혁 ( Lee Jun Hyeog ),최윤성 ( Choe Yun Seong ),정일엽 ( Jeong Il Yeob ) 대한천식알레르기학회 2003 천식 및 알레르기 Vol.23 No.4

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)

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.

Association of DOCK8, IL17RA, and KLK12 Polymorphisms with Atopic Dermatitis in Koreans

( Won Il Heo ),( Kui Young Park ),( Mi-kyung Lee ),( Yu Jeong Bae ),( Nam Ju Moon ),( Seong Jun Seo ) 대한피부과학회 2020 Annals of Dermatology Vol.32 No.3

Background: Early-onset and severe atopic dermatitis (AD) in patients increase the probability of the development of allergic rhinitis or asthma. Treatment and prevention strategies in infants and young children with AD are targeted toward treating the symptoms, restoring skin barrier functions, and reducing the absorption of environmental allergens in an attempt to attenuate or block the onset of asthma and food allergy. Objective: Given that the initiating events in AD remain poorly understood, identifying those at risk and implementing strategies to prevent AD is necessary. Methods: Whole-exome sequencing (WES) was performed in a 43 control group and a disease group with 20 AD patients without atopic march (AM) and 20 with AM. Sanger sequencing was carried out to validate found variants in cohorts. Results: DOCK8, IL17RA, and KLK12 single-nucleotide polymorphisms were identified by WES as missense mutations: c.1289C>A, p.P97T (rs529208); c.1685C>A, p.P562G (rs12484684); and c.457+27>C, rs3745540, respectively. A case-control study show that total immunoglobulin E (IgE) level was significantly increased in the AA genotype of DOCK8 compared to the CA genotype in allergic patients. The rs12484684 of IL17RA increased risk of adult-onset AD (odds ratio: 1.63) compared to the control for (A) allele frequency. AD and AM Patients with the IL17RA CA genotype also had elevated IgE levels. rs3745540 of KLK12 was associated with AD in dominant model (odds ratio: 2.86). Conclusion: DOCK8 (rs529208), IL17RA (rs12484684), and KLK12 (rs3745540), were identified using a new WES filtering method. the result suggests that polymorphism of DOCK8 and IL17RA might be related to increase the total IgE level. (Ann Dermatol 32(3) 197∼205, 2020)

DBA/1JCrj Mouse에 있어서 콜라젠유도관절염에 관한 면역학적 고찰

박승규,이지연,정일엽,최용경,최인성,김효준 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.3

There is growing evidence that a variety of cytokines are secreted by cells at the inflammation sites of rheumatoid arthritis (RA) and that CDS+ B cell, a minor subtype of B cell population producing natural autoantibodies, is implicated in pathogenesis of RA. In this study, we evaluated the both cytokne levels and change of CDS+ B cell population in the peripheral blood from DBA/lJCrj mice(H-2`) which are collagen-induced arthritis(CIA) susceptible strain. Surprisingly, the healthy DBA/1JCrj and MRL/Ipr/Ipr(H-2'`) mice which were autoimmune susceptible strains tested in this experiment, showed lower IL-4, IL-6 and IL-10 levels in serum by 60% than heal-thy normal mouse strains such as Balb/c(H-2d), C57BL/6(H-2') and outbred ICR mice. MRL/lpr/ 1pr mice in which onset of spontaneous autoimmune disease is dependent upon age were similar to healthy DBA/1JCrj mice in levels of the cytokines in the serum when they are young. After the CIA(for DBA/1JCrj) or the spontaneous autoimmune disease(for MRL/lpr/Ipr) had been developed in the susceptible mouse strains, the levels of IL-6 and IL-4 in the serum were increased to 1.8- and 13-fold, respectively, as compaired with those from control groups while level of IL-10 remained relatively constant. The elevated levels of IL-4- and IL-6, however, in the serum from mice with disease status were still below those of the healthy normal mouse strains. On the other hand, CDS+ B cell population in the peripheral blood, which were reported to be increased with the development of RA for human, was rather significantly decreased for the CIA-induced DBA/lJCrj mice as evidenced by FACS analysis. It could be due to the differences in the pathogenic mechanism between CIA and RA. Taken together, our results. suggest that the levels of both these cytokines and CDS+ B cells may be utilized as important diagnostic markers for arthritides.

특발성 염증성 근육병증 환자에서 IL-17 발현의 증가

백승훈 ( Seung Hoon Baek ),이준희 ( Jun Hee Lee ),김근태 ( Geun Tae Kim ),이정욱 ( Joung Wook Lee ),조미라 ( Mi Ra Cho ),김주인 ( Ju In Kim ),이선희 ( Sun Hee Lee ),김대성 ( Dae Seong Kim ),김성일 ( Sung Il Kim ) 대한류마티스학회 2008 대한류마티스학회지 Vol.15 No.2

Objective: Idiopathic inflammatory myopathies (IIMs) are systemic autoimmune diseases characterized by infiltration of T lymphocytes, monocytes, and macrophages in muscle tissues. Interleukin-17 (IL-17), a Th17 cytokine, has potent pro-inflammatory actions and plays a role in autoimmune diseases. We investigated the expression of IL-17 in muscle tissues of patients with IIMs. Methods: We measured the IL-17 mRNA level of muscle tissues from 14 patients with IIMs (9 patients with dermatomyositis and 5 patients with polymyositis) by real-time RT-PCR and compared with controls. We also performed an immunohistochemical stain to detect IL-17 expression. Results: The expressions of IL-17 were significantly enhanced in IIMs than controls. In immunohistochemistry, IL-17 was expressed in perimysial, endomysial and perivascular infiltrating inflammatory cells. Conclusion: These results suggest that IL-17 plays a role in the immunopathogenesis of IIMs.

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.

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.

Interleukin-13 Increases Podocyte Apoptosis in Cultured Human Podocytes

Lee, Keum Hwa,Oh, Ji Young,Seong, Su-Bin,Ha, Tae-Sun,Shin, Jae Il Korean Society of Pediatric Nephrology 2018 Childhood kidney diseases Vol.22 No.1

Purpose: Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. Methods: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). Results: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apoptosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63%, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. Conclusion: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.

금은화(金銀花) 및 금은화전초(金銀花全草)가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향

이동언,이재령,김영우,권영규,변성희,신상우,서성일,권택규,변준석,김상찬,Lee, Dong-Eun,Lee, Jae-Ryung,Kim, Young-Woo,Kwon, Young-Kyu,Byun, Sung-Hui,Shin, Sang-Woo,Suh, Seong-Il,Kwon, Taeg-Kyu,Byun, Joon-Seok,Kim, Sang-Chan 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.2

Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.