Blockade of indoleamine 2,3-dioxygenase protects mice against lipopolysaccharide-induced endotoxin shock.

Jung, In Duk,Lee, Min-Goo,Chang, Jeong Hyun,Lee, Jun Sik,Jeong, Young-Il,Lee, Chang-Min,Park, Won Sun,Han, Jin,Seo, Su-Kil,Lee, Sang Yong,Park, Yeong-Min Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.182 No.5

<P>Suppression of an excessive systemic inflammatory response is a promising and potent strategy for treating endotoxic sepsis. Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan catabolism, may play a critical role in various inflammatory disorders. In this study, we report a critical role for IDO in the dysregulated immune response associated with endotoxin shock. We found that IDO knockout (IDO(-/-)) mice and 1-methyl-D-tryptophan-treated, endotoxin-shocked mice had decreased levels of the cytokines, TNF-alpha, IL-6, and IL-12, and enhanced levels of IL-10. Blockade of IDO is thought to promote host survival in LPS-induced endotoxin shock, yet little is known about the molecular mechanisms that regulate IDO expression during endotoxin shock. In vitro and in vivo, IDO expression was increased by exogenous IL-12, but decreased by exogenous IL-10 in dendritic cells and splenic dendritic cells. Interestingly, whereas LPS-induced IL-12 levels in serum were higher than those of IL-10, the balance between serum IL-12 and IL-10 following challenge became reversed in IDO(-/-)- or 1-methyl-D-tryptophan-treated mice. Our findings demonstrate that the detrimental immune response to endotoxin shock may occur via IDO modulation. Restoring the IL-12 and IL-10 balance by blocking IDO represents a potential strategy for sepsis treatment.</P>

$CD4^+$ Jurkat T 세포주에서 Th1과 Th2 사이토가인 조절에 미치는 황금 유래 Baicalin, Baicalein 및 Wogonin의 효과

김용준,이정치,김홍용,설광화,윤용갑,장선일,Kim Young Jun,Lee Jeong Chi,Kim Hong Yong,Xie Guanghua,Yun Yong Gab,Jang Seon Il 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.3

In the present study, baicalin, baicalein, and wogonin, a major flavone isolated from Scutellaria Radix were examined for their effects on PMA-induced Interlukin-6 (IL-6), $interferon-\gamma(IFN-\gamma)$, tumor necrosis factor $(TNF)-\alpha$, IL-4, IL-10, and IL-13 productions in the PMA-stimulated $CD4^+$ Jurkat T cells. These three compounds inhibited PMA-induced Th1 cytokine $(IL-6,\;IFN-\gamma,\;TNF-\alpha)$ and Th2 cytokine (IL-4 and IL-13) productions in a concentration-dependent manner. But wogonin, but not baicalin baicalein, increased PMA-induced IL-10 production. These results suggest that baicalin, baicalein, and wogonin, a major flavone modulate Th1 and Th2 cytokine productions in $CD4^+$ Jurkat T cells and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

결핵성 흉막염 환자에서 T 임파구 기능 및 IL-2 수용체 표현율에 대한 연구

임건일 ( Gune Il Lim ),김대수 ( Dae Soo Kim ),어수택 ( Soo Taek Uh ),정연태 ( Yun Tae Jung ),우준희 ( Jun Hee Woo ),김용훈 ( Yong Hun Kim ),박춘식 ( Choon Sik Park ) 대한결핵 및 호흡기학회 1990 Tuberculosis and Respiratory Diseases Vol.37 No.3

Immunostimulating Effects of Enzyme Hydrolysate of Ginseng Marc Polysaccharides in Immune-suppressed Mice

( Jeong Yeon Seo ),( Jun Il Kim ),( Seongcheol Kim ),( Gi Eun Park ),( Hyeon Jeong Kim ),( Jisun Lee ),( Jin Ree ),( Yong Il Park ) 한국키틴키토산학회 2018 한국키틴키토산학회지 Vol.23 No.2

Ginseng contains various health-beneficial bioactive compounds, such as ginsenosides and polysaccharides. Despite ginseng marc is produced after the extraction process and usually discarded as wastes, it still contains considerable amounts of potential bioactive compounds, including saponins and polysaccharides. Previously, we reported that glucan type ginseng oligosaccharides obtained by enzyme hydrolysis of ginseng marc-derived polysaccharides exhibit immunostimulatory activities in macrophages and, activated macrophages are in turn capable of inhibiting the growth of skin melanoma cells via induction of apoptosis. In the present study, an enzymatic hydrolysate (GEH) containing these ginseng oligosaccharides was prepared and immune-enhancing activities of GEH were evaluated in vivo using cyclophosphamide-treated immune-suppressed mice. Immunosuppression was induced by 3 day-intraperitoneal (i.p.) injection of cyclophosphamide in mice. When comparedh normal control group, the GEH administered orally for 29 days facilitated the recovery of weight gain, indices of spleen and thymus, and enhanced T lymphocyte and B lymphocyte proliferation, cytokine productions of IL-6, IL-4 and IL-10 in culture supernatants of Con A-treated splenic T lymphocytes, and increased the serum levels of IL-4 and IL-10 as well as NK cell activity. These results demonstrated that administration of GEH stimulates and enhances immune function in immune-suppressed mice. The results of this study suggest that GEH of ginseng marc can be developed as a health-beneficial food material with immunostimulatory activity.

3차 병원의 병동에서 시행된 심폐소생술의 분석

류진호,정경운,위준선,문정미,전병조,문원식,김용권,소정일,허탁,민용일 대한응급의학회 2001 대한응급의학회지 Vol.12 No.4

Background: Although cardiopulmonary resuscitation(CPR) is a very effective therapy in cardiac arrest, it is hard to prove the true effectiveness of CPR. Several studies about out-of-hospital and emergency department CPR exist, but only a few reports about in-hospital CPR are available. This study was designed to investigate in-hospital cardiac arrest, to analyze the result of CPR, and to evaluate the problems associated with in-hospital CPR. Methods: A clinical analysis of 71 cases of in-hospital CPR announcement from January 2000 to August 2000 was performed. The initial rhythm on cardiac arrest, return of spontaneous circulation(ROSC), and the survivals were analyzed in the case of the 46 true cardiac arrest patients. Results: During 8 months, there were 71 cases of in-hospital CPR announcement. Among them, there were 46 cases of true cardiac arrest and 25 cases of non-cardiac arrest. Of the 46 true cardiac-arrest cases, 27(58.7%) experienced ROSC, 15(32.6) survived for over 24 hours, and 7(15.2%) survived to be discharged. The initial rhythms on cardiac arrest were 30 cases(65.2%) of asystole, 14(30.4%) of PEA(pulseless electrical activity), and 2(4.3%) of ventricular fibrillation, with ROSC being 17 cases(56.7%), 9(64.3%) and 1(50.0%) cases and discharged survivors being 4 cases(13.3%), 3(21.4%) and 0(0.0%) cases, respectively. Conclusion: Extraordinarily high proportions of asystole and PEA were seen in the initial rhythm of cardiac arrest, and those were associated with high survival rates. Although further study is needed to evaluate the course leading to this high proportion of asystole and PEA, this result suggests that if the EMS system in the hospital is activated promptly and systematically, a better outcome will be achieved in case of cardiac arrest with asystole and PEA.

Ahnak-knockout mice show susceptibility to Bartonella henselae infection because of CD4+ T cell inactivation and decreased cytokine secretion

( Eun Wha Choi ),( Hee Woo Lee ),( Jun Sik Lee ),( Il Yong Kim ),( Jae Hoon Shin ),( Je Kyung Se ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.4

The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with 2 × 10⁸ colony-forming units of B. henselae Houston-1 on day 0 and subsequently on day 10. Blood and tissue samples of the mice were collected 8 days after the final B. henselae injection. B. henselae infection in the liver of Ahnak-knockout and wild-type mice was confirmed by performing polymerase chain reaction, with Bartonella adhesion A as a marker. The proportion of B. henselaeinfected cells increased in the liver of the Ahnak-knockout mice. Granulomatous lesions, inflammatory cytokine levels, and liver enzyme levels were also higher in the liver of the Ahnak-knockout mice than in the liver of the wild-type mice, indicating that Ahnak deletion accelerated B. henselae infection. The proportion of CD4+interferon-y(IFN-y)⁺ and CD4⁺interleukin (IL)-4⁺ cells was significantly lower in the B. henselae-infected Ahnak-knockout mice than in the B. henselae-infected wild-type mice. In vitro stimulation with B. henselae significantly increased IFN-y and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase IFN-y and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, IL-1α, IL-1β, IL-6, IL-10, RANTES, and tumor necrosis factor-α secretion was significantly elevated in the splenocytes obtained from both B. henselae-infected wild-type and Ahnak-knockout mice. These results indicate that Ahnak deletion promotes B. henselae infection. Impaired IFN-y and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice. [BMB Reports 2019; 52(4): 289-294]

마우스에서 황금 유래 Wogonin의 Th1과 Th2 사이토가인 조절 효과

김용준,이정치,김홍용,설광화,윤용갑,장선일,Kim Young Jun,Lee Jeong Chi,Kim Hong Yong,Xie Guanghua,Yun Yong Gab,Jang Seon Il 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.3

In the present study, wogonin, a major flavone isolated from Scutellaria Radix were examined for its imunosuppressive activity on the 2,4-dinitro-fluorobenzene (DNFB)-induced delayed type hypersensitivity (DTH) in C3H/HeN mice. This compound inhibited selectively $TNF-\alpha$ and IL-4, but not IL-6, IL-10 and $IFN-\gamma$ on DNFB-induced Th1 and Th2 cytokines in a concentration-dependent manner. Interestingly, this compound increased the expression of heme oxygenase-1 (HO-1) in a concentration-dependent manner The above results reveal that wogonin possesses anti-inflammatory, humoral and cellular immunomodulatory, and stress reducing activities on the DNFB-induced DTH in mice and these properties may contribute to the anti-atopic dermatitis activity of Scutellaria Radix.

Effects of Chung-Pae Inhalation Therapy on a Mouse Model of Chronic Obstructive Pulmonary Disease

Hwang, Joon-Ho,Lee, Beom-Joon,Jung, Hee Jae,Kim, Kwan-Il,Choi, Jun-Yong,Joo, Myungsoo,Jung, Sung-Ki Hindawi Publishing Corporation 2015 Evidence-based Complementary and Alternative Medic Vol.2015 No.-

<P>Chung-pae (CP) inhalation therapy is a method frequently used in Korea to treat lung disease, especially chronic obstructive pulmonary disease (COPD). This study investigated the effects of CP inhalation on a COPD animal model. C57BL/6 mice received porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS) alternately three times for 3 weeks to induce COPD. Then, CP (5 or 20 mg/kg) was administered every 2 h after the final LPS administration. The effect of CP was evaluated by bronchoalveolar lavage (BAL) fluid analysis, histological analysis of lung tissue, and reverse transcription polymerase chain reaction analysis of mRNA of interleukin- (IL-) 1<I>β</I>, tumor necrosis factor- (TNF-) <I>α</I>, IL-6, and tumor growth factor- (TGF-) <I>β</I>. Intratracheal CP administration reduced the number of leukocytes and neutrophils in BAL fluid, inhibited the histological appearance of lung damage, and decreased the mRNA levels of the proinflammatory cytokines IL-1<I>β</I>, TNF-<I>α</I>, IL-6, and TGF-<I>β</I>. Intratracheal CP administration effectively decreased the chronic inflammation and pathological changes in a PPE- and LPS-induced COPD mouse model. Therefore, we suggest that CP is a promising strategy for COPD.</P>

Tryptophan Negatively Regulates IgE-mediated Mast Cell Activation

Prashanta Silwal(실왈 프라산타),Keuna Shin(신근아),Seulgi Choi(최슬기),Uk Namgung(남궁욱),Chan Yong Lee(이찬용),Jun-Young Heo(허준영),Kyu Lim(임규),Jong IL Park(박종일),Ki-Hwan Kim(김기환),Seung-Kiel Park(박승길) 대한체질인류학회 2017 해부·생물인류학 (Anat Biol Anthropol) Vol.30 No.2

비만세포는 알레르기 반응을 일으키는 주된 세포로서 항원 자극에 반응하여 알레르기 유발 물질인 히스타민, 단백질 분해효소, 염증성 지질 물질 및 사이토카인 등을 분비한다. 아미노산인 트립토판은 염증반응을 조절한다. 트립토판 투여는 비만세포가 관여하는 염증성 장염 증상을 완화시킨다. 그러나 트립토판이 비만세포의 알레르기 반응에 미치는 영향에 대한 연구는 없다. 본 저자들은 트립토판이 IgE 매개 알레르기 반응에 미치는 영향을 비만세포 수준에서 그리고 실험동물 생쥐에서 연구하였다. IgE-매개 수동 피부 아나필락시스를 생쥐에서 연구하였다. 또한 IgE-매개 비만세포 활성화 반응 즉, 탈과립 반응, 염증성 지질인 LTB4와 사토카인 (TNF-α와 IL-4) 등의 분비를 측정하였다. 트립토판을 생쥐에 복강 주사하면 IgE 매개 수동 피부 아나필락시스를 억제하였다. 또한 비만세포 수준에서도 트립토판은 IgE 매개 알레르기 반응들, 즉 탈과립 반응과 염증성 지질인 LTB4 및 사이토카인인 TNF-α와 IL4의 분비를 억제하였다. 이러한 결과로부터 트립토판은 IgE 매개 알레르기 반응을 세포 수준 및 실험동물 수준에서 억제함을 알 수 있었다. Mast cells are major immune cells in allergy to secrete allergic mediators by a degranulation process and make and secrete inflammatory lipids and cytokines in response to antigen stimulation. An amino acid tryptophan regulates immune functions. Tryptophan ameliorates inflammatory colitis in which mast cells are engaged. However, its effects on mast cells remain to be solved. We investigated the effect of tryptophan on IgE-mediated allergic responses in the mast cells and mice. IgEmediated passive cutaneous anaphylaxis (PCA) in mice were examined. Also IgE-mediated mast cell activation responses such as degranulation of stored granules and secretion of inflammatory lipid LTB4 and cytokines (TNF-α and IL-4) were measured. Intraperitoneal administration of tryptophan suppressed PCA in mice. Also, in the cellular level tryptophan inhibited IgE-mediated mast cell activation such as IgE-mediated degranulation and the production of LTB4. Also, it inhibited production of inflammatory cytokines TNF-α and IL-4. In summary, tryptophan suppressed IgE-mediated allergic activation in vivo and in vitro. Tryptophan supplementation is beneficial for IgE-mediated allergy.

허혈성 흰쥐 해마에서 NMDA수용체 아단위 NR2B와 세포골격단백질 MAP-2의 변화

정용욱,문일수,고복현 동국대학교 경주대학 1996 東國論集 Vol.15 No.-

전반적 저산소증(global ischemia) 과 불완전 국소허혈(incomplete focal ischemia)에서 신경세포의 NMDA수용체 아단위 2B와 세포골격단백질 MAP2의 변화를 알아보기 위하여 immunoblot방법과 면역 조직화학법으로 조사하여 다음과 같은 결과를 얻었다. 1. 해마신경세포의 연접이후치밀질(postsynaptic density, PSD) 를 이용한 NR2B, MAP2표현의 변화를 알아보면 저 산소증과 불완정 국소허혈에서 3일 후 감소 하다가 6일 후에는 점차 정상 수준으로 환원되었으며(저 산소증의 MAP2제외)반대편 해마의 경우 NR2B는 3일경과 후 표현이 감소 하다가 6일 후에는 정상 수준 이상으로 증가 하였으며 MAP2는 정상과 변화가 없었다. 2. 해마의 면역조직화학법에서 MAP2의 표현은 저 산소증과 동측의 불완전 국소허혈 부위의 CA1, CA3, DG 전체 지역에서 정상에 비해 3일 후 감소 하다가 6일 후 증가 하였다(허혈의 반대측 해마의 경우는 CA1에서 MAP2의 표현이 6일째 감소됨.) 이상의 관찰 결과를 종합 해볼때 해마 신경세포의 지연성 손상은 NMDA수용체 아단위 2B의 감소와 세포골격단백질 MAP2를 파괴하며 그 시기는 3일 이전에 일어나 6일경에는 회복하는 단계를 거치는 것으로 생각되며 정확한 회복 시기는 허혈의 정도에 따라 차이가 있을 것으로 생각된다. 또한 허혈 반대편 부위에서의 NR2B와 MAP2의 면역 반응성 감소는 허혈지역의 주변부위에서(penumbra)에서 나타나는 현상과 일치하였다. Changes of NR2B & MAP-2 expression in global and focal ischemia Department of Anatomy, School of Medicine, DongGuk University YONG WOOK JUNG M.D., IL SOO MOON Ph.D., BOK HYUN KO M.D Microtubule associated protein 2 (MAP-2) degradation by Ca2' - dependent proteases after NMDARs (NRs) activation has been postulated in delayed hippocampal neuronal damage.. Degradation of MAP-2 in rat brain after hypoxia and ischemia was investigated through immunoblot analyses and immunohistochemistry. In order to test the changes of each NR subunits (NR2B) and MAP2 in neuronal damage, we carried out in vivo experiments to see if there is selective changes of MAP-2 and NR2B in global hypoxia and focal left common carotid artery ligation.. We found that, in global ischemia, NR2B was down-regulated and recovered to normal level by 3 and 6 days while MAP-2 was unchanged by the same days compared to untreated hippocampus, and that similar changes regarding to NR2B and MAP-2 were observed at ipsilateral hippocampus in focal ischemia. In contralateral hippocampus, NR2B expression was decreased and MAP-2 expression was unchanged compared to untreated hippocampus. These results imply that NR2B and MAP2 expression are regulated on the degree of ischemic damage in delayed neuronal death and that, in focal ischemia, down-regulation of NR2B in contralateral hippocampus may be a similar effect which is seen in the peripheral zone (penumbra) of ischemic region.