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.

자궁내막증 병변에서의 Cytokine mRNA의 발현 양상

이택후(Taek Hoo Lee),김광수(Gwang Soo Kim),김일규(Il Gyu Kim),전상식(Sang Sik Chun),조영래(Young Lae Cho) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.9

목적: 자궁내막증은 최근에 그 빈도가 급격하게 증가되고 있으나 아직까지 병인과 치료법이 확실하게 정립되지 못하고 있는 부인과 내분비의 대표적인 질환이다. 최근 들어서 자궁내막증 환자의 불임의 원인으로 cytokine이 밀접하게 관여됨이 밝혀지고 있고 자궁내막증의 병인으로 복강내로 역류된 월경혈에 의한 복강내의 국소적 염증에 대한 개체의 반응정도와 면역체계의 변화가 중요하게 인정되고 있으나 아직까지 정확한 기전은 밝혀져 있지 않기 때문에 이에 저자는 자궁내막증 환자의 복수 내에서의 cytokine의 정량측정과 골반내 자궁내막증 병변조직에서의 cytokine mRNA의 발현 양상을 조사하여 자궁내막증 환자의 병인분석을 시도하였다. 연구방법: 자궁내막증 진단을 받고 복강경 혹은 개복 수술을 받은 30명의 환자에서 총 60개의 자궁내막증 병변이라고 의심되는 조직을 채취하여 이를 RT-PCR법을 이용하여 Cytokine 유전자의 발현양상을 조사하였다. 또한 7례의 정상대조군과 23례의 자궁내막증 환자의 복수를 ELISA법을 이용하여 정량분석을 시도하였다. 결과: 자궁내막증 환자의 복수내에서 IL-6와 IL-10의 농도는 자궁내막증의 임상적 중증도에 따라서 의미있게 증가되어 있었으나 IFN-γ, TNF-α, IL-1β, 그리고 IL-5의 농도는 정상 대조군에 비해서 변화가 없었다. 모든 예의 심부 자궁내막증 병변조직과 표재성 자궁내막증 병변조직에서 IL-1β cytokine mRNA의 발현을 볼 수 있었다. IL-5와 IL-6은 표재성 병변 12개 중에서 각각 2개의 black lesion에서만 발현을 볼 수 있었으며 IL-10은 표재성 병변에서는 12개중 2개에서 그리고 심부성 병변에서는 8개중 1개의 조직에서만 발현되었다. IFN-γ는 표재성 병변에서는 전혀 발현이 없었으나 심부성 병변에서는 8개중 4개의 조직에서 발현이 되었으며 TNF-α는 표재성 병변에서는 red 및 black 병변에서 각각 1개의 조직에서만 발현이 되었으나 심부성 병변에서는 역시 8개중 4개의 조직에서 발현이 되었다. 결론: 표재성 병변이 골반강내에 착상하여 염증성 반응이 일어날 수 있는 원인이 제공되면 IL-1β 혹은 TNF-α같은 염증성 cytokine이 분비가 되며 이로 인해 생성되는 단핵세포의 chemotactic factor에 의해 대식세포의 증가와 활성화가 이루어지고 이어서 복강내에 IL-6 등의 cytokine이 증가되며 마지막으로 여러 가지 증가된 cytokine에 대한 반대 반응으로 IL-10이 증가됨을 추정할 수가 있겠으며 이러한 가정은 앞으로 cytokine을 이용한 치료적 응용의 기초적인 연구로서 중요한 의미를 제공할 수 있다고 하겠다. Objective: The pathogenesis of endometriosis is generally accepted that retrograde menstruation and alterations in the local pelvic immune environment. This study was performed to help elucidate what kind of role various cytokines might play in the pathogenesis of endometriosis. Method: Concentrations of peritoneal fluid cytokines were compared in 7 women with normal pelvic finding and 23 women with endometriosis by enzyme-linked immunosorbent assay(ELISA). The patterns of cytokine mRNA expression in 8 ovarian endometrioma and 12 superficial pelvic endometriosis lesions were investigated by reverse transcription-polymerase chain reaction(RT-PCR) amplification method. Result: Both IL-6 and IL-10 levels in peritoneal fluid specimens with endometriosis tended to be higher than normal. However, there were no significant differences between peritoneal fluid concentrations of IFN-γ, TNF-α, IL-1β, and IL-5 of women with and without endometriosis. The levels of IL-6 and IL-10 were significantly higher in peritoneal fluid of women with severe endometriosis compared to women with mild endometriosis. IL-1β mRNA was expressed in all of 8 deep and 12 superficial endometriosis lesions. IL-5 and IL-6 mRNA were expressed in only two black lesions respectively, however, both were not expressed in the all deep lesions. Expressions of IL-10 mRNA occurred in one red and one black lesion while this was expressed in only one of the deep lesions. TNF-α mRNA was expressed in one red and one black lesion of 12 superficial lesions compared with four of the deep lesions. There was the difference between kinds of increased cytokines in the peritoneal fluid and those of expressed cytokines in the endometriotic lesions of patients with endometriosis. Conclusion: This study supports the concept that local immunologic factors may be important in the pathogenesis and pathophysiology of endometriosis. The pattern of cytokine mRNA expression of endometriotic lesions would seem to indicate that proinflammatory cytokines such as IL-1β and TNF-α are responsible for the development or progression of endometriosis.

Two-Track Medical Treatment Strategy According to the Clinical Scoring System for Chronic Rhinosinusitis

Kim, Dong-Kyu,Kang, Seong Il,Kong, Il Gyu,Cho, Young Hoon,Song, Seul Ki,Hyun, Se Jin,Cho, Sung Dong,Han, Sang-Yoon,Cho, Seong-Ho,Kim, Dae Woo The Korean Academy of Asthma, Allergy and Clinical 2018 Allergy, Asthma & Immunology Research Vol.10 No.5

<P><B>Purpose</B></P><P>The previously reported Japanese clinical scoring study (JESREC) suggests that chronic rhinosinusitis (CRS) can be divided into 4 subtypes according to the degree of eosinophilic CRS (ECRS) and offers the information regarding the prognosis of CRS to clinicians. However, this scoring system has not yet been validated by an immunological study and needs to provide treatment guidelines based on underlying immunologic profiles. We investigated the immunologic profile of each CRS subgroup according to the JESREC classification and suggest its clinical application.</P><P><B>Methods</B></P><P>A total of 140 CRS patients and 20 control subjects were enrolled. All patients were classified into 4 groups according to the JESREC (non-, mild, moderate and severe ECRS). Nasal tissues were analyzed for mRNA expression of major cytokines (IL-5, IL-10, IL-13, IL-17A, IL-22, IL-23p19, IFN-γ, periostin, thymic stromal lymphopoietin [TSLP] and ST2), major chemokines (CCL11, CCL24, CXCL1 and CXCL2), transcription factors (T-bet, GATA3, RORC and FOXP3) and COL1A1 for type I collagen. Protein levels of 3 major cytokines (IL-5, IL-17A and IFN-γ) were also measured by multiplex immunoassay. Principal component analysis (PCA) was conducted to investigate the overall profile of multiple mediators.</P><P><B>Results</B></P><P>The moderate/severe ECRS showed up-regulation of type 2-related mediators (IL-5, IL-13, periostin, TSLP and ST-2), whereas INF-γ (type 1 cytokine) and CXCL1 (neutrophil chemokine) expressions were increased in non-/mild ECRS compared with moderate/severe ECRS. The JESREC classification reflected an immunological endotype. In PCA data, PCA1 indicates a relative type 2 profile, whereas PCA2 represents a type 1/type 17-related profile. In this analysis, mild ECRS was indistinguishable from non-ECRS, whereas moderate to severe ECRS showed a distinct distribution compared with non-ECRS. The JESREC classification could be divided into 2 categories, non-/mild vs. moderate/severe ECRS based on underlying immunological analyses.</P><P><B>Conclusions</B></P><P>The CRS clinical scoring system from the JESREC study reflects an inflammatory endotype. However, the immunologic profile of mild ECRS was similar to that of non-ECRS. Therefore, we propose type 2-targeted medical treatment for moderate to severe ECRS and type 1/type 17-targeted for non-ECRS and mild ECRS as the first treatment option.</P>

주조직적합항원이 불일치하는 마우스 동종 조혈모세포이식에서 IL-2로 유도된 CD4+CD25+ T세포를 이용한 이식편대숙주병의 억제

현재호,정대철,정낙균,박수정,민우성,김태규,최병옥,김원일,한치화,김학기,Hyun, Jae Ho,Jeong, Dae Chul,Chung, Nak Gyun,Park, Soo Jeong,Min, Woo Sung,Kim, Tai Gyu,Choi, Byung Ock,Kim, Won Il,Han, Chi Wha,Kim, Hack Ki 대한면역학회 2003 Immune Network Vol.3 No.4

Background: In kidney transplantation, donor specific transfusion may induce tolerance as a result of some immune regulatory cells against the graft. In organ transplantation, the immune state arises from a relationship between the immunocompromised graft and the immunocompetent host. However, a reverse immunological situation exists between the graft and the host in hematopoietic stem cell transplantation (HSCT). In addition, early IL-2 injections after an allogeneic murine HSCT have been shown to prevent lethal graft versus host disease (GVHD) due to CD4+ cells. We investigated the induction of the regulatory CD4+CD25+ cells after a transfusion of irradiated recipient cells with IL-2 into a donor. Methods: The splenocytes (SP) were obtained from 6 week-old BALB/c mice ($H-2^d$) and irradiated as a single cell suspension. The donor mice (C3H/He, $H-2^k$) received $5{\times}10^6$ irradiated SP, and 5,000 IU IL-2 injected intraperitoneally on the day prior to HSCT. The CD4+CD25+ cell populations in SP treated C3H/He were analyzed. In order to determine the in vivo effect of CD4+CD25+ cells, the lethally irradiated BALB/c were transplanted with $1{\times}10^7$ donor BM and $5{\times}10^6$ CD4+CD25+ cells. The other recipient mice received either $1{\times}10^7$ donor BM with $5{\times}10^6$ CD4+ CD25- cells or the untreated SP. The survival and GVHD was assessed daily by a clinical scoring system. Results: In the MLR assay, BALB/c SP was used as a stimulator with C3H/He SP, as a responder, with or without treatment. The inhibition of proliferation was $30.0{\pm}13%$ compared to the control. In addition, the MLR with either the CD4+CD25+ or CD4+CD25- cells, which were isolated by MidiMacs, from the C3H/He SP treated with the recipient SP and IL-2 was evaluated. The donor SP treated with the recipient cells and IL-2 contained more CD4+CD25+ cells ($5.4{\pm}1.5%$) than the untreated mice SP ($1.4{\pm}0.3%$)(P<0.01). There was a profound inhibition in the CD4+CD25+ cells ($61.1{\pm}6.1%$), but a marked proliferation in the CD4+CD25- cells ($129.8{\pm}65.2%$). Mice in the CD4+CD25+ group showed low GVHD scores and a slow progression from the post-HSCT day 4 to day 9, but those in the control and CD4+CD25- groups had a high score and rapid progression (P<0.001). The probability of survival was 83.3% in the CD4+CD25+ group until post-HSC day 35 and all mice in the control and CD4+CD25- groups died on post-HSCT day 8 or 9 (P=0.0105). Conclusion: Donor graft engineering with irradiated recipient SP and IL-2 (recipient specific transfusion) can induce abundant regulatory CD4+CD25+ cells to prevent GVHD.

운동의 항암효과와 암 치료를 위한 보조요법으로서 운동처치

정일규(Il Gyu Jeong),오명진(Myung Jin Oh) 한국사회체육학회 2010 한국사회체육학회지 Vol.0 No.40

It has been reported that regular exercise has the effect to reduce the risk of cancer and exercise intervention help the cancer patient to be able to get through the hard treatment procedure. In this study, the author summarized the proposed mechanisms of anti-cancer and anti-fatigue effects of exercise and introduce the exercise intervention researches so for. For the proposed anti-cancer effect of exercise, three major mechanism have been suggested as follows. The first, exercise-induced reactive oxygen species(ROS) might cause the apoptosis of pre-stage of cancer cells. The second, ROS or pro-inflammatory cytokines like IL-1 and TNF-α which can be induced by exercise might activate the signaling pathway to promote the transcription of endogenous anti-oxidant enzymes such as SOD, CAT, GPX and HSP70 and in turn increase the protective capability of our body against various carcinogenic factors. The third, Regular exercise can increase the phase Ⅱ enzymes such as GST and UDP-GT associating with DNA repair system and also increase the activities of proteasome and OGG1 which have the role of eliminating the misfolding protein or oxidized base of DNA, respectively. It also has been reported that cancer-related fatigue(CRF) might be the most common and painful side effect of cancer itself and cancer treatment such as chemical and radiation therapy or transplantation surgery. The increase of pro-inflammatory cytokines during the cancer treatment has been suggested as the most plausible etiology of CRF. The anemia induced by the decreased function of erythropoiesis in red bone marrow and deregulation of HPA axis and the abnormal change of synaptic serotonin level in central nerve system might be caused by chronically increased pro-inflammatory cytokines. Many researches which have investigated the effects of exercise intervention for cancer patients and survivors suggested that exercise might be one of the most effective way to alleviate the cancer-related fatigue and prevent the change of body composition and the decrease of muscle mass and strength, cardiovascular function and improve the pain index and quality of life(QOL). Therefore we need to encourage the cancer specialist to use the exercise intervention for cancer treatment as the most evidence-based intervention and cooperate to improve the treatment effect and quality of life(QOL) of cancer patients and survivors.

Scoparone from Artemisia capillaris Inhibits the Release of Inflammatory Mediators in RAW 264.7 Cells upon Stimulation Cells by Interferon-γ Plus LPS

Seon Il Jang,Young-Jun Kim,Woo-Yiel Lee,Kyung Chell Kwak,Seung Hwa Baek,Gyu Beum Kwak,Young-Gab Yun,Tae-Oh Kwon,Hun Taeg Chung,Kyu-Yun Chai 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.2

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin E2 (PGE2) upon stimulation by IFN-γ/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-γ/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and PGE2 in macrophages by inhibiting iNOS and COX-2 expression.

An optimized peptide vaccine strategy capable of inducing multivalent CD8 ⁺ T cell responses with potent antitumor effects

Cho, Hyun-Il,Jung, Soo-Hyun,Sohn, Hyun-Jung,Celis, Esteban,Kim, Tai-Gyu TaylorFrancis 2015 Oncoimmunology Vol.4 No.11

<P>Therapeutic cancer vaccines are an attractive alternative to conventional therapies for treating malignant tumors, and successful tumor eradication depends primarily on obtaining high numbers of long-lasting tumor-reactive CD8<SUP>+</SUP> T cells. Dendritic cell (DC)-based vaccines constitute a promising approach for treating cancer, but in most instances low immune responses and suboptimal therapeutic effects are achieved indicating that further optimization is required. We describe here a novel vaccination strategy with peptide-loaded DCs followed by a mixture of synthetic peptides, polyinosine-polycytidylic acid (poly-IC) and anti-CD40 antibodies (TriVax) for improving the immunogenicity and therapeutic efficacy of DC-based vaccines in a melanoma mouse model. TriVax immunization 7–12 d after priming with antigen-loaded DCs generated large numbers of long-lasting multiple antigen-specific CD8<SUP>+</SUP> T cells capable of recognizing tumor cells. These responses were far superior to those generated by homologous immunizations with either TriVax or DCs. CD8<SUP>+</SUP> T cells but not CD4<SUP>+</SUP> T cells or NK cells mediated the therapeutic efficacy of this heterologous prime-boost strategy. Moreover, combinations of this vaccination regimen with programmed cell death-1 (PD-1) blockade or IL2 anti-IL2 antibody complexes led to complete disease eradication and survival enhancement in melanoma-bearing mice. The overall results suggest that similar strategies would be applicable for the design of effective therapeutic vaccination for treating viral diseases and various cancers, which may circumvent current limitations of cell-based cancer vaccines.</P>

Scoparone from Artemisia capillaris Inhibits the Release of Inflammatory Mediators in RAW 264.7 Cells upon Stimulation Cells by Interferon-${\gamma}$ Plus LPS

Jang Seon Il,Kim Young-Jun,Lee Woo-Yiel,Kwak Kyung Chell,Baek Seung Hwa,Kwak Gyu Beum,Yun Young-Gab,Kwon Tae-Oh,Chung Hun Taeg,Chai Kyu-Yun The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.2

Scoparone is a major component of the shoot of Artemisia capillaris (Compositae), which has been used for the treatment of hepatitis and biliary tract infection in oriental countries. In the present study we observed that, scorparone exhibited no cytotoxic effect in unstimulated macrophages, but reduced the release of nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ upon stimulation by IFN-${\gamma}$/LPS or LPS. The inhibitory effects were found to be in conjuction with the suppression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in IFN-${\gamma}$/LPS stimulated RAW 264.7 cells. Moreover, scoparone also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. These results suggest that scoparone decreases the production of the inflammatory mediators such as NO and $PGE_2$ in macrophages by inhibiting iNOS and COX-2 expression.

The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis

Jung, Joo Hyun,Kang, Il Gyu,Kim, Dae Young,Hwang, You Jin,Kim, Seon Tae The Korean Society of Ginseng 2013 Journal of Ginseng Research Vol.37 No.2

Korean red ginseng (KRG) is reported to have anti-allergic properties, including beneficial effects on asthma and atopic dermatitis. However, its effect on allergic rhinitis has not been studied extensively. This study examined how KRG affected allergic inflammation of the nasal cavity in an allergic mouse model. A total of 40 Balb/c female mice were divided into four experimental groups according to treatment and allergic state: group 1 (G1), saline only; group 2 (G2), ovalbumin (OVA); group 3 (G3), OVA+KRG; and group 4 (G4), OVA+dexamethasone. Serum IgE levels were significantly lower in the KRG treatment group (G3) than in the allergic group (G2). However, serum IgG1 levels did not differ between G2 and G3. In the nasal lavage fluid, IL-4 and IL-5 levels were significantly lower in G3 than in G2 (p<0.05). H&E and Luna staining revealed that the eosinophil count was lower in G3 and G4 than in G2 (p<0.05). Immunohistochemical staining revealed that there were fewer IL-4-, IL-5-, and MUC5AC-positive cells in G3 and G4 than in G2 (p<0.05). These results indicate that KRG reduces the nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines.

The effect of Korean red ginseng on allergic inflammation in a murine model of allergic rhinitis

Joo Hyun Jung,Il Gyu Kang,Dae Young Kim,You Jin Hwang,Seon Tae Kim 고려인삼학회 2013 Journal of Ginseng Research Vol.37 No.2

Korean red ginseng (KRG) is reported to have anti-allergic properties, including beneficial effects on asthma and atopic dermatitis. However, its effect on allergic rhinitis has not been studied extensively. This study examined how KRG affected allergic inflammation of the nasal cavity in an allergic mouse model. A total of 40 Balb/c female mice were divided into four experimental groups according to treatment and allergic state: group 1 (G1), saline only; group 2 (G2), ovalbumin (OVA); group 3 (G3), OVA+KRG; and group 4 (G4), OVA+dexamethasone. Serum IgE levels were significantly lower in the KRG treatment group (G3) than in the allergic group (G2). However, serum IgG1 levels did not differ between G2 and G3. In the nasal lavage fluid, IL-4 and IL-5 levels were significantly lower in G3 than in G2 (p<0.05). H&E and Luna staining revealed that the eosinophil count was lower in G3 and G4 than in G2 (p<0.05). Immunohistochemical staining revealed that there were fewer IL-4-, IL-5-, and MUC5AC-positive cells in G3 and G4 than in G2 (p<0.05). These results indicate that KRG reduces the nasal allergic inflammatory reaction in an allergic murine model by reducing Th2 cytokines.