Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration

Bae, Gi-Sang,Kim, Dong-Goo,Jo, Il-Joo,Choi, Sun-Bok,Kim, Myoung-Jin,Shin, Joon Yeon,Kim, Dong-Uk,Song, Ho-Joon,Joo, Myungsoo,Park, Sung-Joo ELSEVIER 2019 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.69 No.-

<P><B>Abstract</B></P> <P>Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 μg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Desoxo-narchinol-A (DN) is a natural compound of HO-1 inducer in pancreas. </LI> <LI> Mechanism of DN-induced HO-1 is mediated by MAPK/Activator Protein-1/HO-1 signaling. </LI> <LI> DN-induced HO-1 blocks neutrophil infiltration into pancreas via inhibition of CXCL2. </LI> <LI> DN inhibits cerulein-induced acute pancreatitis (AP) and AP-associated lung injury. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

서울의 Penicillinase Producing Neisseria gonorrhoeae 발생빈도(1998)

김재홍,김준호,반재용,이정우,황성주,정준규,정성태,강진문,조흔정,홍창의,정혜신,이한승,김이선,이봉길,이종호,선영우,한기덕,윤성필,이성훈,안종성,박석범,문승현,조항래,김형섭,류지호,황재영,박준홍,손상욱 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

In recent years, gonorrhea has been pandemic and remains one of the most common STDs in the world, especially in developing countries. For the detection of a more effective therapeutic regimen and assessing the prevalence of Penicillinase Producing Neisseria gonorrhoeae(PPNG), we have been trying to study the patients who have visited the Venereal Disease Clinic of Choong-Ku Public Health Center in Seoul since 1980 by menas of the chromogenic cephalosporin method. In 1998, 93 strians of N. genorrhoeae were isolated, among which 60(64.5%) were PPNG. The prevalence of PPNG in Seoul, which had been decreased to 39% in 1996 after a peak of 74.3% in 1993, is increased to 64.5% in 1998.

서울의 PPNG 발생 빈도(1991-1992)

김재홍,윤기범,박평원,김영진,전경민,김영태,김중환,곽호,구상완,송민석,유옥,지혜구,김동원,문상은,박영립,정승호,성범진,성순제,엄주용,황정열,이기홍,이주협,전태진 대한화학요법학회 1994 대한화학요법학회지 Vol.12 No.1

The prevalence of PPNG among pretreated gonorrhea cases isolated at the STD clinic of Choong-Ku Public Health Center in Seoul has been studied and reported annually since 1981. In 1991, 123 strains of N.gonorrhoeae were isolated, among which 58(47.1%) were PPNG. In 1992, 98 starains of N.gonorrhoeae were isolated, among which 51(52.0%) were PPNG. In all, 109(49.3%) strains were found to be PPNG among 221 strains isolated between 1991-1992. The prevalence of PPNG in Seoul showed increased tendency till 1989, thereafter, it has been stationary or slightly decreasing.

Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-κB activation

( Sun-uk Bak ),( Suji Kim ),( Hae-jun Hwang ),( Jung-a Yun ),( Wan-sung Kim ),( Moo-ho Won ),( Ji-yoon Kim ),( Kwon-soo Ha ),( Young-guen Kwon ),( Young-myeong Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Heme oxygenase (HO-1) catalyzes heme to carbon monoxide (CO), biliverdin/bilirubin, and iron and is known to prevent the pathogenesis of several human diseases. We assessed the beneficial effect of heme degradation products on osteoclastogenesis induced by receptor activator of NF-κB ligand (RANKL). Treatment of RAW264.7 cells with CORM-2 (a CO donor) and bilirubin, but not with iron, decreased RANKLinduced osteoclastogenesis, with CORM-2 having a more potent anti-osteogenic effect. CORM-2 also inhibited RANKLinduced osteoclastogenesis and osteoclastic resorption activity in marrow-derived macrophages. Treatment with hemin, a HO-1 inducer, strongly inhibited RANKL-induced osteoclastogenesis in wild-type macrophages, but was ineffective in HO-1^+/-cells. CORM-2 reduced RANKL-induced NFATc1 expression by inhibiting IKK-dependent NF-κB activation and reactive oxygen species production. These results suggest that CO potently inhibits RANKL-induced osteoclastogenesis by inhibiting redox-sensitive NF-κB-mediated NFATc1 expression. Our findings indicate that HO-1/CO can act as an antiresorption agent and reduce bone loss by blocking osteoclast differentiation. [BMB Reports 2017; 50(2): 103-108]

서울의 Penicillinase Producing Neisseria Gonorrhoeae 발생빈도(1996)

김재홍,황동규,전재홍,김윤석,김중환,김용준,이창균,임동진,김현수,조창근,김경문,박상훈,전우형,김희성,이호정,차명수,김갑형,김형석,김석우,황지환,박병순,권오상,이민수,송기훈,성소영,이인섭,부태성 대한화학요법학회 1999 대한화학요법학회지 Vol.17 No.2

Background : In recent years, gonorrhea has been panedemic and remains one of the most commom STDs in the world, especially in developing countries. Objective & Methods: For the detection of a more effective therapeutic regimen and assessing the prevalence of PPNG, we have been trying to study the patients who have visited the VD Clinic of Choong-Ku Public Health Center in Seoul since 1980 by means of the chromogenic cephalosporin method. Results: In 1996, 139 strains of N. gonorrhoeae were isolated, among which 53(39.0%) were PPNG. Conclusion: Our results suggests that after a peak of 74.3% in 1993, the prevalence of PPNG in Seoul is gradually declining.

PGA2-induced expression of HO-1 is mediated by transcriptional upregulation of Nrf2

Sang-sun Lee,Yun-Jeong Choe,Hyein Lee,Sun-Young Lee,Ho-Shik Kim 대한독성 유전단백체 학회 2019 Molecular & cellular toxicology Vol.15 No.2

Backgrounds: Prostaglandin (PG) A2 reportedly stimulated expression of heme oxygenase (HO)-1 at the level of transcription via the activation of p38MAPK. Details of the mechanism, however, have not been provided, and this includes identification of the transcription factors responsible for PGA2-induced HO-1 expression. Herein is described an analysis of the role of nuclear factor erythroid 2 related factor 2 (Nrf2) and how PGA2 increases the activity of Nrf2 during PGA2-induced HO-1 expression. Methods: Expressions of HO-1 and Nrf2 were analyzed at the levels of both mRNA and protein. Nrf2 siRNA, SB203580, an inhibitor of p38MAPK, and scavengers of reactive oxygen species (ROS) were used to identify the effects of Nrf2, p38MAPK and ROS on PGA2-induced HO-1 expression. Results: Although SB203580 suppressed PGA2-induced HO-1 expression, genetic activation of p38MAPK could not stimulate the transcription of HO-1. Cycloheximide (CHX), an inhibitor of protein translation, almost completely prevented PGA2-induced increase of HO-1 transcription, but it did not prevent the phosphorylation of p38MAPK, which suggests that both de novo protein synthesis and p38MAPK activity are required to induce the transcription of HO-1 in response to PGA2 treatment. In addition, PGA2 increased the level of both Nrf2 mRNA and protein in a dose-dependent manner. Knockdown of Nrf2 using small interfering RNA (siRNA) suppressed PGA2-induced HO-1 expression. The PGA2-induced transcription of Nrf2 was prevented by ROS scavengers such as n-acetyl-l-cysteine and tempol but not CHX. Furthermore, siRNA against p38MAPK did not change the level of nuclear Nrf2 protein. Conclusion: These findings suggest that PGA2 induces HO-1 transcription via an increase in Nrf2 protein, the transcription of which is initiated by an accumulation of ROS that is independent of the p38MAPK activation pathway.

腫瘍의 화학요법과 放射線療法의 副作用에 대한 韓方藥物療法

곽계호,김성훈,임낙철 대한동의병리학회 1995 동의생리병리학회지 Vol.9 No.2

연구배경 : 국내 질병에 의한 사망률중 암에 의한 것이 최상위를 차지하고 있으며 또한 그 비율이 점차 증가추세에 있다. 지금까지 국내외에서 암의 예방과 치료법에 대하여 대규모 연구가 진행되어 많은 함암제가 개발되었으나 여러 부작용이 나타나면서 최근에는 암의 치료를 극대화하면서 여러 항암치료의 부작용을 감소시키기 위한 생약 및 한약에 대한 연 구가 활발히 진행되고 있어, 저자는 향후한약을 이용한 실험연구와 임상에 기여하고자 제 관련 문헌을 정리 조사하여 보고하게 되었다. 방법 : 한의학에서의 연구동향과 암치료에 널리 활용되고 있는 화학료법 및 방사선료법의 부작용감소를 위한 한방약물료법에 관해 한의학의 중요서적과 잡지를 중심으로 정리하고 비교 고찰하였다. 결과 : 종양치료에 활용된 치법으로는 부정법(扶正法)과 거사법(祛邪法)으로 크게 나눌수 있는데 부정법에 활용된 약물로는 삼류와 백출, 황기, 복령, 감초, 자감초, 당귀, 백작약, 생지황, 숙지황 등의 약물이 선용되었으며, 거사약물로는 백화사설초, 반지련, 석상백외 18종 이 주로사용되었고, 종양치료에 실험 및 임상에서 유효하였던 처방은 화류탕등을 비롯 다 양한 처방이 면역 기능을 증강시켜 부작용감소 및 병용투여에서 상승효과를 나타냈다. To be helpful to the treatment of cancer with oriental medicine, we got clinical report together and analyzed the data. The results were obtained as follows; 1. The treating methods could be summarized as two methods that were reinforcing vital energy and eliminating harmful Qi; The methods of reinforcing vital energy were reinforcing spleen and increasing Qi; reinforcing spleen and harmonize stomach, aid virility and nourishing blood, nourishing stomach and incresing body fluid, reinforcing kidney and strength the basic energy, warmth kidney and aid virility. The other methods of eliminating poison were transforming pathological fluid and softening activating blood, transforming pathological blood, guiding Qi, take off and harmonize harmful body fluid, disperse Qi and dry the dampness, transforming pathological blood and harmonize moisture. 2. The oriental herbs used for reinforcing vital energy were Radix Ginseng, Codonops is Pilosulae Radix, Radix Pseudostellariae, Adenophorae Radix, Scrophulariae Radix, Astractylodis Macrocephalae Rhizoma, Astragali Radix, Poria, Gylcyrrhizae Radix, Angelicae Gigantis Radix, Paeonilae Radix Alba, Rehmanniae Radix and used for eliminating harmful Qi were Oldenlindiae Diffusae Herba, Herba Scutellariae Barbatae, Paridis Rhizoma, Verbenae Herba, Smilacis Chlnae Rhizoma, Radix Semiaquilegiae, Houttuynae Herba et. 3.The useful prescriptions used for cancer therapy were Hwalyutang Yukmijihwangtang, Yonghosinchonghwan, Bokbangkyokolamtang, Yikki-sojeungbang, Samchobujeonhangamchungjye and Bokbangkyokolamtang, Yikksojeungbang were reported to be effective in immunodulatory reaction and Bokbangsamsahapjye, Sibjeondaeboang, Gagyulpijukyeotang, Hwayebokwontang showed the combined treatment with anticancer drug was effective and Hangamlyeong(抗癌靈) was effective for pain caused by cancer. 4.The useful antitumor effective prescriptions in experimental investi-sation were Yikikeonbihabjye, Keon biiksinchungjye, Bisinbang, Sankyeol pyeolpyeon, Hangamdanhyeokkeombokbang, Janglyupyeong, HangamIIho, Keonbiyikitang, Yikkiisojingbang, Sakunjatang, Bokbanggyongkyejusayek, Bujeonghangambang, Bokbangjungyakjusayek, Yukmijihwangtang, Samchobujeonghangamchungjae, Samkijusayek, Yikkiyanghyeolbowonkyonang, Samyongtang-Bojungikkitang, Soyinibo-jungikang among them Bisinbang, keonbiiksinchungjye, Janglyup-yeong, Keonbiyikitang, Yikkisojingbang, Yukmijihwangtang, Keumku-esinkihwan were showed antitumor effect by regulate immunity function. 5. The main treatment for the side effect by chemotheraphy was reinforcing Qi, spleen and harmonize stomach and Omisodokyeum, Hyangsaynkkunjatang, Yijintang, Kamlosodokdan, Silbiyeum, Hageojye-johwan, Sibjeondaebotang, Olyeongsan, Sobanhakaboklyeongtang, seung-baektang, Bisinbang, Keonbiyiksinbang, Sambaekdangjang, Bokbang-samsahabjye, Keonbiyikitang, Janganseungbaekchungjye, Kobonkeoe I ho, Bokihwawejikubang, Bokbangsaenghyeolyeng, Keonbiyikkibosinbang, Hwangbaekhabjye, Yukkunjatang, Seonbokdaejatang, Bangdoktang, Hwangjeongomibang, seunghyeoltang, Kilpijukyetang, Sakunjatang, Yikkibohy-eolkeonbitang, Kangyeoktang,Samkijusayaek, Bujeongseungbaektang, Yukmijihwanghwan, were suggested for the side effect by chemotheraphy. 6. The main treatment for the side effect by radiotheraphy was increasing Yin and clarifying heat, Sasammaekmundongtang, Boyeum-jeon, Maekmundongyeum, Dangkwibohyeltang, Paljintang, Bowontang, Yukkunjatang, Pyeongwesan, samintang, Kwakrakhalywongtang, Cheon-keumwekyeongtang, Sohamhamhyungtang, Paljeongsan, Sokyeoyeumja, Kalkeunkeumlyeongtang, Yeonlitang, Yilkwanjeon Oklyeojeon, Yukmijihwangtang, Hwangiyeontang, Hwanglyeonhaedoktang, Yangyeumcheongpyeoko, Yidongko, Chuliko, Cheongpyeotang, Jayeumkanghwatang, Hangbiyinam I ho, Hangbiyinam II ho, Hangbiyinam III ho, Hangbyinam IV ho, Jukyeoseokkotang, Samsatang I ho, Samsatang II ho, Samsatang, Bokbanggsaenghyeollyeng, Bujeongsaengjintang, Yikkiyangyeumbang, Sinlibpyeon, Sakunjatang, Sakunjatang, Kobonyik-kitang, keoehaedoktang, Bujeongjeunghyohabjye, were suggested for the side effect by radiotheraphy. 7. The useful prescription for the side effect by chemotheraphy and radiotherapy in experimental investigation were Hwangbaekhabjye, Sakunjatang, Yikkibohyeolkeonbitang, Bujeongsaengjintang, Samchobu

Gliotoxin ameliorates TNBS-induced colitis through regulation of NF-kB, and up-regulation of HO-1

김상욱 ( Kim Sang Ug ),( Jay Min Oh ),( Yeon Hwa Kim ),( Jung Moo Hur ),( Kyo Sang Yoo ),( Yong Sung Kim ),( Joo Jin Yeom ),( Tae Hyeon Kim ),( Suck Chei Choi ),( Chang Duk Jun ),( Yong Ho Nah ) 대한소화기학회 2003 대한소화기학회 추계학술대회 Vol.2003 No.-

<Background & aims> During inflammation in colon, cells of the gut mucosa produce or express various inflammatory mediators, including IL-8, TNF-a and IL-1b, and intercellular adhesion molecule 1 (ICAM-1). These cytokines and chemokines have recently been

Negative Regulation of Hypoxic Responses via Induced Reptin Methylation

Jason S. Lee,김윤호,김익수,김보규,최희준,이지민,신희재,김정화,김지영,서상범,이호,Olivier Binda,Or Gozani,Gregg L. Semenza,김민형,김근일,황대희,백성희 Sookmyung Women's University Research Institute of 2010 여성과 건강 Vol.6 No.1

Clinicopathological role of kidney injury molecule-1 in immunoglobulin A nephropathy

( Yu Ho Lee ),( Yang-gyun Kim ),( Sang-ho Lee ),( Ju-young Moon ),( Kyung-hwan Jeong ),( Tae-won Lee ),( Chun-gyoo Ihm ) 대한신장학회 2014 Kidney Research and Clinical Practice Vol.33 No.3

Background: Urinary kidney injury molecule-1 (KIM-1) is an early and sensitivebiomarker of acute kidney injury, but it is unclear if it is a biomarker of chronicglomerulonephritis. We evaluated whether urinary KIM-1 levels in patients withimmunoglobulin A (IgA) nephropathy can be a marker to reflect clinicopathologicalseverity and predict the prognosis. Methods: We measured urinary KIM-1 levels in 40 patients (15 males; mean age36.6712.9 years) with IgA nephropathy and 10 healthy people (5 males; mean age37.379.6 years) as controls. The correlation of urinary KIM-1 levels with patients’clinical parameters, histological grades, and follow-up data were analyzed using themodified H. S. Lee grading system and tubulointerstitial change scores. Results: Urinary KIM-1 levels were higher in patients with IgA nephropathy thanhealthy controls (P¼0.001). Univariate and multivariate regression analyses showedthat urinary KIM-1 levels had a direct correlation with H. S. Lee grade andtubulointerstitial inflammation (P¼0.004 and P¼0.011, respectively). Conclusion: In patients with IgA nephropathy, urinary KIM-1 has a significantcorrelation with histopathologic severity.