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 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.

Nrf2-Heme oxygenase-1 modulates autophagy and inhibits apoptosis triggered by elevated glucose levels in renal tubule cells

Joo Heon Kim,김경민,Jin Uk Jeong,Jong-Ho Shin,신재민,방기태 대한신장학회 2019 Kidney Research and Clinical Practice Vol.38 No.3

Background: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. Methods: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. Results: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. Conclusion: The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

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

Stain improvement in the white button mushroom ‘Seolgang’ and its varietal characteristics in Agaricus bisporus

Byung-Joo Lee,Mi-Ae Lee,Yong-Gyun Kim,Kwang-Won Lee,Yong-Pyo Lim,Byung-Eui Lee,Ho-Yeon Song 한국버섯학회 2012 한국버섯학회지 Vol.10 No.4

The button mushroom (Agaricus bisporus) is one of the most widely cultivated important edible mushroom species. In the breeding of new button mushroom, ‘Seolgang’ was developed by crossing two monokaryons ‘CM020913-27’ and ‘SSU423-31’. Because of the secondarily homothallism, only a small percentage of the basidia produce 3 or 4 spores, which are mostly haploid (n) and do not fruit. Single spore cultures derived from these types of spores produce a vegetative mycelium that also contain a variable number of genetically identical nuclei per cell called monokaryon. The lack of clamp connections between monokaryon and dikaryon required a series of mycelial culture and fruiting test. After crossing, hybrids were cultivated on a small scale and on a commercial scale at a farm. For this, the spawn was made by a commercial spawn producer and the spawned compost by a commercial compost producer. Mycelial growth of ‘Seolgang’ on CDA was better at 20℃ and 25℃ when it was compared with that of ‘505 Ho’. The mature cap shape of new strain ‘Seolgang’ is oblate spheroid and the immature cap shape is round to oblate spheroid. The cap diameter was 41.2 mm on average. In comparison with white strain ‘505 Ho’, the strain had a yield that was 9% higher. It produced fruiting bodies which had a higher weight on average per fruiting body and were 19% firmer with a good shelf life. Days of fruiting body were 3-4 days later than those of ‘505 Ho’. The physical characteristics such as elasticity, chewiness, adhesiveness were better than that of ‘505 Ho’. Genetic analysis of the new strain ‘Seolgang’ showed different profiles compared to ‘505 Ho’, CM02913-27, SSU413-31, when RAPD primers A02 and O04 were used.

건조 상추 에탄올 추출물의 항염증 활성

이은주(Eun-Joo Lee),서유미(Yu-Mi Seo),김용현(Yong-Hyun Kim),정정욱(Chungwook Chung),성화정(Hwa-Jung Sung),손호용(Ho-Yong Sohn),박종이(Jong-Yi Park),김종식(Jong-Sik Kim) 한국생명과학회 2019 생명과학회지 Vol.29 No.3

상추는 가장 선호하는 녹색 채소 중 하나이다. 상추는 폴리페놀성 화합물을 비롯한 다양한 성분을 함유하고 있으며, 항균, 항산화, 항염증 등의 생리활성을 가지고 있는 것으로 알려져 있다. 본 연구에서는 건조상추의 에탄올 추출물(DLE)을 제조하고 이들의 항염증 활성을 연구하였다. DLE의 항염증 활성을 측정하기 위하여 LPS로 활성화된 마우스 대식세포 RAW 264.7 세포주에서 nitric oxide (NO) 생성을 측정하였다. DLE는 세포주의 생존에는 영향을 미치지 않으면서 NO 생산을 현저하게 저해하였다. DLE에 의해 염증 유전자인 iNOS와 COX-2의 유전자와 단백질의 발현이 모두 감소하였으며, 6개의 염증관련 cytokine 유전자(IL-1α, IL-1β, IL-1F6, TNF-α, CSF2, 그리고 CXCL10)의 발현이 모두 감소하였다. 또한, DLE의 처리는 MAPKs 경로의 인산화를 모두 저해하였으며, NF-κB p65의 핵으로의 이동을 저해하였다. 이러한 결과는 DLE의 항염증 활성은 MAPKs 경로와 NF-κB 경로를 조절함으로써 이루어짐을 시사한다. 또한, DLE는 농도의존적으로 reactive oxygen species (ROS)의 생산을 저해하였으며, hemeoxygenase-1 (HO-1) 단백질의 발현을 증가시켰으며, HO-1의 전사조절인자인 Nrf2의 핵으로의 이동을 증가시켰다. 결론적으로, 이러한 연구결과는 DLE가 염증관련 유전자의 발현을 감소시키며, MAPKs, NF-κB, 그리고 Nrf2/HO-1 등 다양한 경로를 조절함으로써 항염증 활성을 가지는 것을 제시한다. Lettuce (Lactuca sativa L.) is one of the most popular green leafy vegetables, and it contains various beneficial components including polyphenolic compounds and has been known to possess various biological functions such as anti-microbial, anti-oxidative, and anti-inflammatory activities. In the present study, we prepared ethanol extract of dried lettuce (DLE) and investigated its anti-inflammatory activity. To evaluate the anti-inflammatory activity of DLE, nitric oxide (NO) production was measured in LPS-activated mouse macrophage RAW 264.7 cells. DLE significantly suppressed NO production in these cells without affecting cell viabilities while resveratrol was used as a positive control. DLE dramatically decreased the expression of pro-inflammatory genes such as iNOS and COX-2 at the mRNA and protein levels and reduced the expression of several cytokines including IL-1α, IL-1β, IL-1F6, TNF-α, CSF2 and CXCL10. In addition, DLE suppressed phosphorylation of MAPKs and the nuclear translocation of NF-κB p65 indicating DLE shows its anti-inflammatory activity via regulating MAPKs pathway and NF-κB pathways. And also, DLE reduced the production of reactive oxygen species in a dose-dependent manner. DLE increased HO-1 protein expression, and also increased the nuclear translocation of Nrf2. Overall, our results suggest that lettuce down-regulate various pro-inflammatory genes and have its anti-inflammatory activity via regulating MAPKs, NF-κB, and Nrf2/HO-1 pathways.

연잎, 연자육, 연자방 에탄올 추출물의 항염증 활성

이은주(Eun-Joo Lee),서유미(Yu-Mi Seo),김용현(Yong-Hyun Kim),정정욱(Chungwook Chung),성화정(Hwa-Jung Sung),손호용(Ho-Yong Sohn),박종이(Jong-Yi Park),김종식(Jong-Sik Kim) 한국생명과학회 2019 생명과학회지 Vol.29 No.4

연은 아시아 국가에서 음식과 약재로 널리 사용되는 재료이다. 본 연구에서는 연의 잎(leaf, NL), 자육(seed, NS), 자방(seedpod, NSP)으로부터 에탄올 추출물을 제조하고 이들의 항염증 활성과 작용기전을 규명하였다. 이들의 항염증 활성을 연구하기 위하여 LPS로 자극된 RAW 264.7 세포에서 nitric oxide (NO) 생산을 측정하였다. NL, NS, NSP는 세포 생존율에 영향을 주지 않으면서, 농도의존적으로 NO의 생산을 현저하게 저해하였으며, iNOS 및 COX-2와 같은 pro-inflammatory 중재자들의 단백질 발현을 감소시켰다. 또한, NL, NS, NSP는 MAPKs 단백질의 인신화를 감소시키고 NF-κB p65의 핵으로의 이동을 저해함으로써, 세 추출물에 의한 항염증 활성은 MAPKs 경로와 NF-κB 경로를 조절함으로써 이루어짐을 제시한다. 게다가, ROS의 생성이 세 추출물에 의해서 모두 저해되었으며, HO-1의 발현과 HO-1의 전사조절인자인 Nrf2의 핵으로의 이동이 증가되었다. 결론적으로, 이러한 연구결과는 연의 다양한 부위의 추출물인 NL, NS 그리고 NSP는 항염증 활성을 가지고 있으며, MAPKs, NF-κB, Nrf2/HO-1 등 다양한 신호경로를 통해 조절할 수 있음을 제시한다. Nelumbo nucifera, also known as sacred lotus, has mainly been used as a food throughout the Asian countries. In the present study, we prepared ethanol extracts from leaf (NL), seed (NS), and seedpod (NSP) of Nelumbo nucifera and investigated their anti-inflammatory activities in mouse macrophage RAW 264.7 cells. To evaluate the anti-inflammatory activities of NL, NS, and NSP, nitric oxide (NO) production was measured in LPS-stimulated RAW 264.7 cells. NL, NS, and NSP significantly reduced NO production in a dose-dependent manner without affecting cell viabilities. NL, NS, and NSP dramatically decreased the protein expression of pro-inflammatory genes such as iNOS and COX-2. NL, NS, and NSP also suppressed phosphorylation of MAPKs and the nuclear translocation of NF-κB p65 indicating they have their anti-inflammatory activities via regulating mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) pathways. In addition, we analyzed the production of reactive oxygen species (ROS) by the treatment of NL, NS, and NSP. All extracts reduced ROS production in a dose-dependent manner. And also, they increased heme oxygenase-1 (HO-1) protein expression and the nuclear translocation of nuclear respiratory factor 2 (Nrf2). In conclusion, our results suggest that Nelumbo nucifera has its anti-inflammatory activity via regulating MAPKs, NF-κB, and Nrf2/HO-1 pathways.

사과 추출물과 phloretin에 의한 항염증 활성

김근호(Geun-Ho Kim),이은주(Eun-Joo Lee),류승민(Seung-Min Ryu),손호용(Ho-Yong Sohn),김종식(Jong-Sik Kim) 한국생명과학회 2021 생명과학회지 Vol.31 No.2

본 연구에서는 풋사과의 열수추출물(GAHW)과 에탄올추출물(GAE), 그리고 애사과 열수추출물(UAHW)을 제조하고 LPS로 활성화된 RAW264.7세포주를 이용하여 이들의 항염증 활성을 연구하였다. 모든 추출물이 세포생존율에는 영향을 미치지 않고 nitric oxide (NO) 생산을 저해하였으며, iNOS의 발현도 감소시켰다. 반면, UAHW만이 COX-2의 발현을 저해하였다. 또한 모든 추출물이 모든 MAPKs의 인산화를 감소시켰다. 모든 추출물이 ROS의 생산을 농도의존적으로 감소시켰으며, GAHW와 GAE에 의해 HO-1의 발현이 증가됨을 확인하였다. 또한, 사과 flavonoid인 phloretin과 phloridzin의 항염증 활성을 연구하였다. Phloretin은 농도의존적으로 NO의 생산을 저해하였으나, phloridzin은 NO 생산에 아무 영향이 없었다. 또한, phloretin은 iNOS와 COX-2 단백질의 발현을 감소시킨 반면, phloridzin은 두 단백질 발현에 영향을 주지 못하였다. 따라서, 이러한 연구결과는 사과 추출물은 MAPK 경로와 HO-1 경로를 조절함으로써 항염증 활성을 가지며, phloretin이 사과의 항염증 활성을 담당하는 파이토케미칼의 하나가 될 수 있음을 제시한다. In the present study, we prepared hot water extracts of green apple (GAHW) and unripe apple (UAHW), and ethanol extract of green apple (GAE), and investigated their anti-inflammatory activities in LPS-activated RAW264.7 cells. All extracts dramatically suppressed nitric oxide (NO) production in a dose-dependent manner in LPS-stimulated RAW264.7 cells without affecting cell viability. In addition, all extracts decreased the expression of iNOS, whereas UAHW only reduced the expression of COX-2. All extracts suppressed the phosphorylation of MAPKs (p38, ERK, and JNK) indicating all extracts show their anti-inflammatory activities via regulating MAPK pathway. Furthermore, all extracts reduced the production of reactive oxygen species in a dose-dependent manner and they increased the expression of heme oxygenase-I (HO-I) whereas UAHW could not. We also investigated whether apple flavonoids phloretin and phloridzin can have their anti-inflammatory activities in same in vitro model. Phloretin dramatically decreased NO production in a dose dependent manner without affecting cell viability, whereas phloridzin have no effects. Phloretin also reduced the expression of iNOS as well as COX-2, whereas phloridzin could not. Overall, these results suggest that apple extracts have their anti-inflammatory activities via regulating MAPKs and HO-1 pathways, and apple flavonoid phloretin can be one of phytochemicals responsible for anti-inflammatory effect of apple.

Adenovirus-mediated heme oxygenase-1 gene transfer to neonatal porcine islet-like cluster cells: the effects on gene expression and protection from cell stress

염혜정,Han Ro,Sol Ji Park,Ju Ho Hong,Bumrae Cho,김화정,Sung Joo Kim,황종익,이병천,안규리,양재석 한국바이오칩학회 2012 BioChip Journal Vol.6 No.1

Porcine islet xenotransplantation is a promising strategy for the treatment of diabetes that overcomes donor shortages. However, islet xenografts are susceptible to oxidative stress and apoptosis. Heme oxygenase-1 (HO-1) has been shown to protect cells from oxidative stress, apoptosis and inflammation. Here, we investigated whether introduction of human HO-1 (hHO-1) into neonatal porcine islet-like cell clusters (NPCCs) can induce beneficial transcriptional changes in NPCCs against cellular stress. NPCCs were transduced with either adenovirus-HO-1 (Ad-HO-1) or control adenovirus-GFP (Ad-GFP). After treatment with hydrogen peroxide (H2O2) for 24 hours, nitrite oxide (NO) production assays were performed to detect oxidative stress. Microarray analysis was performed using a pig oligonucleotide 44 K gene chip. We profiled transcriptional changes to apoptosis, oxidant and inflammatory genes, and real-time PCR analysis was also performed to confirm the microarray results. Survival of NPCCs after treatment with H2O2 was significantly higher in the Ad-HO-1 group (p⁄0.001), and NO production also decreased in the Ad-HO-1 group (p⁄0.01). The microarray results showed that the expression of pro-apoptosis genes such as CASP3, CASP7, CASP10, CIDE-B and CIDE-C was significantly decreased in the Ad-HO-1 virus group (CASP10; p⁄0.05, CASP3, CIDE-C; p⁄0.01, CASP7, CIDE-B; p⁄0.001). We also found that the expression of oxidative stresses genes including COX1, COX2, CYB5A, SDHD and NOS2 was decreased, and that the anti-oxidant genes Gpx1 and SOD2 were increased in the Ad-HO-1 group (NOS2; p⁄0.05, COXI, COX2, CYB5A, SDHD, SOD2, GPX1; p⁄0.001). However, inflammatory gene expression was not significantly changed. Realtime PCR analysis confirmed the results of the microarray analysis. These results shed light on the underlying mechanisms of the protective effects of hHO-1 on porcine islets from cellular stresses and suggest that hHO-1 could be a promising target gene for the production of transgenic pigs that confer improved islet xenograft survival.

악관절 융기 증강술을 통한 습관성 악관절 탈구환자의 치험례

김일규,신주호,오성섭,최진호,김형돈,오남식,김의성 대한악안면성형재건외과학회 2000 Maxillofacial Plastic Reconstructive Surgery Vol.22 No.2

Recurrent mandibular dislocation is frequent morbidity of temporomandibular joint relatively. There are many etiologic causes in TMJ disorders but, difficult to find obvious one. Various treatment methods have been utilized for a mandibular dislocation. It is categorized into two groups broadly - nonsurgical or surgical methods. The basic rationale of the surgical method is to allow free movement of the condyle by reducing height of articular eminence or to limit anterior excessive movement of the condyle by increasing height of articular eminence or soft tissue anchoring procedure. In this case, 69 year-old woman was treated by augmentation of the articular eminence with mandibular symphysial bone graft leading to osteosynthesis without difficulty. As a result, favorable postoperative outcome was obtained functionally without any complication or recurrence.