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

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.

Chronological changes in inflammatory cytokines immunoreactivities in the mouse hippocampus after systemic administration of high dosage of tetanus toxin.

Yan, Bing Chun,Park, Joon Ha,Kim, In Hye,Shin, Bich Na,Ahn, Ji Hyeon,Yoo, Ki-Yeon,Lee, Deuk-Sik,Kim, Myong Jo,Kang, Il-Jun,Won, Moo-Ho Springer-Verlag 2012 Experimental brain research Vol.223 No.2

<P>Tetanus toxin (TeT) is an exotoxin and has a capacity for neuronal binding and internalization. In the present study, we compared changes in the immunoreactivities and protein levels of interleukin (IL-) 2 as a pro-inflammatory cytokine and IL-4 as an anti-inflammatory cytokine in the hippocampus proper (HP) and dentate gyrus (DG) after systemic treatment of 10 or 100?ng/kg TeT into mice. In this study, we could not find any neuronal damage or loss in any subregions of the hippocampus after TeT treatment. In the control groups, strong IL-2 immunoreactivity was shown in the stratum pyramidal (SP) of the HP and in the granule cell layer (GCL) of the DG. At 6?h post-treatment, IL-2 immunoreactivity was hardly detected in the SP and GCL; however, strong IL-2 immunoreactivity was shown in the stratum oriens of the HP in both the groups. Thereafter, intermediate IL-2 immunoreactivity was shown in the SP and GCL. On the other hand, intermediate IL-4 immunoreactivity was detected in the SP and GCL of the control groups. At 6?h post-treatment, IL-4 immunoreactivity in the SP and GCL was apparently increased. Thereafter, IL-4 immunoreactivity was lower than that at 6?h post-treatment. In brief, IL-2 and 4 immunoreactivities were easily detected in SP and GCL in the controls and dramatically decreased and increased at 6?h post-treatment, respectively.</P>

GATA-3 is a Key Factor for Th1/Th2 Balance Regulation by Myristicin in a Murine Model of Asthma

이규,이창민,정인덕,정영일,천성학,박희주,최일환,안순철,신용규,이상율,염석란,김종석,박영민,Lee, Kyu,Lee, Chang-Min,Jung, In-Duk,Jeong, Young-Il,Chun, Sung-Hak,Park, Hee-Ju,Choi, Il-Whan,Ahn, Soon-Cheol,Shin, Yong-Kyoo,Lee, Sang-Yull,Yeom, S Korean Society of Life Science 2007 생명과학회지 Vol.17 No.8

Myristicin은 육두구에서 발견되는 고농축 정유 중 하나인 물질이다. 하지만 Th1/Th2 면역반응에서 육두구의 항알레르기 효과는 아직 밝혀지지 않았다. 최근에 Th1/Th2 전사인자로서 T-bet, GATA-3가 밝혀졌는데 이번 실험에서 myristicin이 ovalbumin(OVA)으로 유도한 천식(asthma) 생쥐모델에서 Th1,Th2 싸이토카인과 유전자 발현을 조절할 수 있는가에 대하여 알아보았다. 또한 기관지 폐포 세척액을 회수하여 백혈구의 수적 변화, 제2형 협조T세포(Th2 cell)가 생산하는 IL-4, IL-5의 생산에 미치는 영향과 폐조직에서 matrix metalloproteinase (MMP)-9 활성을 측정하였다. 그 결과 기관지 폐포 세척액에서 OVA로 감작하여 천식을 유도한 실험군에서는 호산구의 현저한 증가, Th2 형 싸이토카인(IL-4, IL-5)의 증가가 관찰되었다. 그러나 myristicin을 투여한 그룹에서는 OVA의 감작에 의하여 증가한 각종 염증성 지표들이 감소하거나 정상화 되었다. 또한 OVA에 의하여 증가된 기도저항성이 myristicin 투여에 의하여 감소하였으며 폐조직의 염증성 소견도 뚜렷하게 감소되었다. 이와 같은 연구 결과는 myristicin이 천식의 치료에 유용하게 쓰일 수 있음을 시사해준다. Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

Anti-inflammatory Activity of 1-docosanoyl Cafferate Isolated from Rhus verniciflua in LPS-stimulated BV2 Microglial Cells

Lee, Jae-Won,Cheong, Il-Young,Kim, Hae-Sung,Lee, Jae-Jun,Lee, Yong-Suk,Kwon, Yong-Soo,Kim, Myong-Jo,Lee, Hee-Jae,Kim, Sung-Soo,Chun, Wan-Joo The Korean Society of Pharmacology 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.1

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as protection of neuronal cells against excitotoxicity, the biological activity of 1-docosanoyl cafferate (DC) has not been examined. The objective of the present study was to evaluate the anti-inflammatory effects of DC, isolated from the stem bark of Rhus verniciflua, on lipopoly-saccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of cells with DC significantly attenuated LPS-induced NO production, and mRNA and protein expression of iNOS in a concentration-dependent manner. DC also significantly suppressed LPS-induced release of cytokines such as TNF-${\alpha}$ and IL-$1{\beta}$. Consistent with the decrease in cytokine release, DC dose-dependently and significantly attenuated LPS-induced mRNA expression of these cytokines. Furthermore, DC significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB induced by LPS stimulation was significantly suppressed with DC pretreatment. Taken together, the present study suggests that DC exerts its anti-inflammatory activity through the suppression of NF-kB translocation to the nucleus.

한국인 원발성 사구체신염에서의 IL-1β, IL-1Ra, TNF-α 유전자 다형성에 관한 연구

박미나 ( Mi Na Park ),강양일 ( Yang Il Kang ),이상열 ( Sang Youl Rhee ),정래익 ( Lae Ik Jeong ),나승연 ( Seung Yeon Na ),정경환 ( Kyung Hwan Jeong ),이상호 ( Sang Ho Lee ),이태원 ( Tae Won LEE ),임천규 ( Chun Gyoo Ihm ) 대한신장학회 2006 Kidney Research and Clinical Practice Vol.25 No.2

Anti-allergic effects of a nonameric peptide isolated from the intestine gastrointestinal digests of abalone (Haliotis discus hannai) in activated HMC-1 human mast cells

KO, SEOK-CHUN,LEE, DAE-SUNG,PARK, WON SUN,YOO, JONG SU,YIM, MI-JIN,QIAN, ZHONG-JI,LEE, CHANG-MIN,OH, JUNGHWAN,JUNG, WON-KYO,CHOI, IL-WHAN Spandidos Publications 2016 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.37 No.1

<P>The aim of the present study was to examine whether the intestine gastrointestinal (GI) digests of abalone [Halioti s discus hannai (H. discus hannai)] modulate inflammatory responses and to elucidate the mechanisms involved. The GI digests of the abalone intestines were fractionated into fractions I (>10 kDa), 11 (5-10 kDa) and III (<5 kDa). Of the abalone intestine GI digests (AIGIDs), fraction III inhibited the passive cutaneous anaphylaxis (PCA) reaction in mice. Subsequently, a bioactive peptide [abalone intestine GI digest peptide (AIGIDP)] isolated from fraction III was determined to be 1175.2 Da, and the amino acid sequence was found to be PFNQGTFAS. We noted that the purified nonameric peptide (AIGIDP) attenuated the phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-induced histamine release and the production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta and IL-6 in human mast cells (HMC-1 cells). In addition, we also noted that AIGIDP inhibited the PMACI-induced activation of nuclear factor-kappa B (NF-kappa B) by suppressing I kappa B alpha phosphorylation and that it suppressed the production of cytokines by decreasing the phosphorylation of JNK. The findings of our study indicate that AIGIDP exerts a modulatory, anti-allergic effect on mast cell-mediated inflammatory diseases.</P>

Anti-inflammatory Activity of 1-docosanoyl Cafferate Isolated from <I>Rhus verniciflua</I> in LPS-stimulated BV2 Microglial Cells

Jae-Won Lee,Il-Young Cheong,Hae-Sung Kim,Jae Jun Lee,Yong-Suk Lee,Yong-Soo Kwon,Myong-Jo Kim,Hee Jae Lee,Sung-Soo Kim,Wanjoo Chun 대한생리학회-대한약리학회 2011 The Korean Journal of Physiology & Pharmacology Vol.15 No.1

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as protection of neuronal cells against excitotoxicity, the biological activity of 1-docosanoyl cafferate (DC) has not been examined. The objective of the present study was to evaluate the anti-inflammatory effects of DC, isolated from the stem bark of <i>Rhus verniciflua</i>, on lipopoly</I>saccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of cells with DC significantly attenuated LPS-induced NO production, and mRNA and protein expression of iNOS in a concentration- dependent manner. DC also significantly suppressed LPS-induced release of cytokines such as TNF-Ձ and IL-1Ղ. Consistent with the decrease in cytokine release, DC dose-dependently and significantly attenuated LPS-induced mRNA expression of these cytokines. Furthermore, DC significantly suppressed LPS-induced degradation of IKB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB induced by LPS stimulation was significantly suppressed with DC pretreatment. Taken together, the present study suggests that DC exerts its anti-inflammatory activity through the suppression of NF-kB translocation to the nucleus.

Sargassum horneri inhibits psoriasis-related inflammation in HaCaT keratinocytes and ameliorates imiquimod-induced psoriasis-like skin lesions in mice

Mi-Jin Yim,Jeongmin Lee,Seok-Chun Ko,Hyun-Soo Kim,Jeong Min Shin,Ji Yul Kim,Dae-Sung Lee,Il-Whan Choi 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Sargassum horneri exhibits broad bioactive properties. However the anti-psoriatic effects of its have not been reported. The present study evaluated whether ethanol extract of S. horneri (ESH) can improve the symptoms of psoriasis in vitro and in vivo and elucidated the mechanisms underlying those effects in vitro. ESH treatment significantly attenuated the protein levels of IL-6, IL-8, and TNF-α in IFN-γ/TNF-α stimulated HaCaT keratinocytes. In addition, ESH inhibited (PI3K)/Akt phosphorylation and NF-κB activation in HaCaT keratinocytes. We further demonstrated that the ESH significantly ameliorates the severity of skin lesions (erythema, scaling, and thickness) in the IMQ-induced psoriasis-like mouse model. ESH attenuated the production of inflammatory cytokines by inhibiting Akt/NF-κB signaling pathways in IFN-γ/TNF-α-induced HaCaT keratinocytes. Furthermore, ESH could ameliorate the severity of skin lesions in an IMQ-induced psoriasis-like mouse model. Thus, S. horneri has considerable potential in the treatment or prevention of inflammatory disorders, such as psoriasis.

반복적 관절내 출혈이 관절 활막과 연골 세포의 변화에 미치는 영향

유명철(Myung Chul Yoo),조윤제(Yoon Jae Cho),김강일(Kang Il Kim),전성욱(Sung Wook Chun),소동혁(Dong Hyuk So),조형준(Hyung Jun Cho),양형인(Hyung-In Yang),이상훈(Sang-Hoon Lee),이연아(Yeon-Ahn Lee) 대한정형외과학회 2008 대한정형외과학회지 Vol.43 No.3

목적: 혈액의 관절강내 반복주사 동물 모델을 이용하여, 혈우병성 관절염에서 활막의 변화와 연골 파괴에 대한 병리 기전과 경과 과정을 연구하였다. 대상 및 방법: 뉴질랜드 백색 토끼 수컷 20마리에 18주간 1주 3회씩 귀에서 자가 혈액을 채취하여 우측 슬관절에 1 ㎖를 주사하고, 좌측 슬관절에 생리식염수 1㎖를(대조군) 주사하였다. 11주 후와 18주 후에 양측 슬관절의 X선 촬영을 시행하였고, 활액막과 연골을 채취하여 조직검사를 시행하였다. 활막 세포 배양에서 RT PCR를 이용한 cytokine의 변화를 관찰 하였고, 연골 세포를 추출 배양하여 GAG 및 PGE₂, MMP-1,3 생성을 측정하였다. 결과: 11주째 육안적 변화는 없었으나, 우측 슬관절의 활액막은 조직학적으로 경한 증식반응과 형질세포 및 단핵세포의 활액막내 침착을 보이며 약간의 염증 소견을 나타냈다. 단순 방사선 소견상 특이 소견은 발견되지 않았다. 18주 후에는 육안적으로 우측 슬관절이 좌측에 비하여 부어 있었고, 단순 방사선학적 소견에서는 관절의 퇴행성 변화가 관찰 되었다. 병리학적 소견은 활막의 심한 증식과 염증세포의 침윤이 관찰되었다. 활막의 real-time RT PCR 시행결과 TNF-alpha, IL-1, MMP-1 mRNA 발현이 증가되었다. 연골세포 배양에서 대조군과 비교시 GAG 생성은 감소하고 PGE₂는 증가하였으며 MMP-1과 MMP-3는 변화가 없었다. 결론: 반복적인 관절 내 출혈은 활막세포를 자극하여 활막의 심한 증식과, proinflammatory cytokines의 생성을 증가시키며, 이는 연골 세포의 재생을 억제하고 연골세포의 염증을 증가시켜 연골의 대사기능이 억제되면서 퇴행성 변화를 촉진하여 점차적으로 관절염으로 이행되는 것으로 사료된다. Purpose: We designed this study to demonstrate the pathophysiology of hemophilic arthropathy (HA) by creating an animal model for determining the effect of repeated intraarticular bleeding in the synovium and articular cartilage. Materials and Methods: 20 normal male New Zealand white rabbits were used for this study. We injected 1 ㎖ of autologous blood from the ear vein of the rabbits into the right knee joint three timeds a week for 18 weeks, and we injected 1 ㎖ of normal saline into the left knee joint three times a week for 18 weeks as a control group. We examined the pathologic changes by microscopy and plain X-ray, and we determined the mRNA expression of proinflammatory cytokines in the synovium of the HA by performing real time RT-PCR at the 11<SUP>th</SUP> week and 18<SUP>th</SUP> week after starting blood-injection. We also examined the GAG and the PGE2 production in cultured chondrocytes that were extracted from the HA knees. Results: At the 11<SUP>th</SUP> week, after blood injection there were no remarkable gross changes in the HA knees and the control knee joints. At the 18<SUP>th</SUP> weeks, the experimental knee joints (HA knees) showed grossly swelling and degenerative changes by X-ray. The infiltration of inflammatory cells and the synovial proliferation in the HA knee joints were compared with that in the control knee joints by microscopic examination. The expressions of the mRNA of TNF-alpha, IL-1, MMP-1 and MMP-3 in the HA synovium were increased, as determined by real time RT-PCR, as compared with that in the control knee. In the cultured chondrocytes, the GAG production was decreased and the PGE2 was increased, but the MMP-1 and MMP-3 were not changed, as determined by ELISA. Conclusion: Our results showed that the GAG production of chondrocytes of the HA knees was decreased and there was increased PGE2, so that the cartilage degeneration by intra-articular bleeding was caused by the decreased metabolism of chondrocytes rather than by increased catabolism of the chondrocytes. We suggest that HA was associated with synovitis and cartilage degeneration, but decreased cartilage metabolism was the major mechanism of HA.