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>

The Role of Cyclosporine and Mycophenolate in an Orthotopic Porcine-to-Rat Corneal Xenotransplantation

Lee, Hyeon Il,Kim, Mee Kum,Oh, Joo Youn,Ko, Jung Hwa,Lee, Hyun Ju,Wee, Won Ryang,Lee, Jin Hak The Korean Academy of Medical Sciences 2008 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.23 No.3

<P>We performed this study to investigate the feature of rejection in porcine-to-rat corneal orthotopic transplantation and to evaluate the effect of cyclosporine and mycophenolate on the xeno-rejection. Orthotopic corneal transplantation was done at 91 Sprague-Dawley rats, and they were divided into 10 groups based on the combination of immunosuppressants including dexamethasone, cyclosporine, and mycophenolate mofetil. Graft survival was analyzed and grafted eyes were examined with Hematoxylin & Eosin and CD4 or CD8 staining. Enzyme-linked immunosorbent assays were done for interleukin-2 (IL-2), IL-4, IL-5, IL-10, and interferon (IFN)-γ in cornea, lacrimal gland, and cervical lymph nodes. The longest median survival of the immune suppressant group was 11.00±1.96 days, which showed no statistical differences compared with that of control (8.00±1.52 days). The neutrophils were prominent in the early phase but soon gave way to the monocytes. The number of CD8+ cells was higher than that of CD4+ cells. IL-2 and IFN-γ markedly increased at 10 to13 days in cornea, lacrimal glands, and cervical lymph nodes, which showed a decrease with immunosuppressants except in the cornea. In conclusion, cyclosporine and mycophenolate could not prevent the rejection in porcine to rat orthotopic corneal xenograft associated with infiltraton of CD8+ and innate immune cells.</P>

Anti-inflammatory effect of polyphenol-rich extract from the red alga Callophyllis japonica in lipopolysaccharide-induced RAW 264.7 macrophages

Ryu, BoMi,Choi, Il-Whan,Qian, Zhong-Ji,Heo, Soo-Jin,Kang, Do-Hyung,Oh, Chulhong,Jeon, You-Jin,Jang, Chul Ho,Park, Won Sun,Kang, Kyong-Hwa,Je, Jae-Young,Kim, Se-Kwon,Kim, Young-Mog,Ko, Seok-Chun,Kim, G The Korean Society of Phycology 2014 ALGAE Vol.29 No.4

Despite the extensive literature on marine algae over the past few decades, a paucity of published research and studies exists on red algae. The purpose of this study was to evaluate the potential therapeutic properties of the ethanol extract of the red alga Callophyllis japonica against lipopolysaccharide (LPS)-stimulated macrophage inflammation. The C. japonica extract (CJE) significantly inhibited the nitric oxide (NO) production and the induced dose-dependent reduction of the protein and mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, the CJE reduced the mRNA levels of inflammatory cytokines, including tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6. We investigated the mechanism by which the CJE inhibits NO by examining the level of mitogen-activated protein kinases (MAPKs) activation, which is an inflammation-induced signaling pathway in macrophages. The CJE significantly suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38 MAPK. Taken together, the results of this study demonstrate that the CJE inhibits LPS-induced inflammation by blocking the MAPK pathway in macrophages.

Pulmonary inflammation caused by silica dioxide nanoparticles in mice via TXNIP/NLRP3 signaling pathway

Je‑Oh Lim,Je‑Won Ko,Tae‑Yang Jung,Woong‑Il Kim,So‑Won Pak,In‑Sik Shin,Won‑Kee Yun,Hyoung‑Chin Kim,Jeong‑Doo Heo,Jong‑Choon Kim 대한독성 유전단백체 학회 2020 Molecular & cellular toxicology Vol.16 No.3

Background Silica dioxide nanoparticles (SiONPs) have been used for various medical applications, including therapeutics and imaging, and the use of SiONPs has increased gradually over the years. However, despite an increase in the use of SiONPs, not much is known about mechanism of action of SiONPs and their pulmonary toxicity. Objective The present study investigated the pulmonary toxicity of SiONPs and explored the underlying mechanism of action, primarily focusing on thioredoxin-interacting protein (TXNIP)/NOD-like receptor pyrin domain-containing 3 (NLRP3) in SiONPs-treated mice. We investigated the toxic effects of SiONPs in the lung of BALB/c mice administered 5, 10, and 20 mg/kg SiONPs for 3 days. Results Exposure to SiONPs markedly increased inflammatory cell counts, including those of neutrophils and macrophages, and levels of inflammatory mediators, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in a dose-dependent manner in the bronchoalveolar lavage fluid. Moreover, the inflammation was verified upon histopathological analysis. In addition, exposure to SiONPs increased the expression of TXNIP in a dose-dependent manner and, in turn, upregulated NLRP3 inflammasome proteins, which subsequently induced IL-1β production. Conclusion Collectively, exposure to SiONPs induced inflammation in the lungs of mice, which resulted in the activation of IL-1β production via the TXNIP-NLRP3 axis. Our results provide useful information on the pulmonary toxicity induced by SiONPs and provide insights into the underlying mechanism of action.

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)의 첨가가 생쥐 수정란의 발생과 착상관련 유전자 발현에 미치는 영향

김동훈,고덕성,이회창,이호준,강희규,김태전,박원일,김세웅,Kim, Dong-Hoon,Ko, Duck-Sung,Lee, Hoi-Chang,Lee, Ho-Joon,Kang, Hee-Gyoo,Kim, Tai-Jeon,Park, Won-Il,Kim, Seung-Samuel 대한생식의학회 2002 Clinical and Experimental Reproductive Medicine Vol.29 No.2

Objective : The purpose of the current series of experiments were to assess the effect of GM-CSF, as a medium supplement, on the development of mouse embryos and the expression of LIF and IL-1? mRNA. Materials and Methods: Mouse 2-cell embryos were collected from the oviducts of 6 weeks old ICR mice at 48 hours after hCG injection. Embryos were cultured in P-1 medium supplemented with mouse GM-CSF (0, 1, 5, 10 ng/ml). The embryo development to blastocysts and hatching blastocysts was assessed and the cell number in blastocyst was also examined. Using RT-PCR, the expressions of LIF and IL-1? mRNA in blastocyst were evaluated in the GM-CSF supplemented group and control group. Results: In mouse, the addition of GM-CSF increased the percentage of blastocysts (65.5%, 68.6%, 73.0% and 76.1% for control and 1, 5 and 10 ng/ml, respectively), and increased the proportion of hatching blastocysts (35.2%, 36.4%, 43.2% and 53.0% for control and 1, 5 and 10 ng/ml, respectively). The mean cell numbers in blastocyst were significantly increased in GM-CSF supplemented groups compared to control group. LIF and IL-1? expression in blastocyst were significantly higher in GM-CSF supplemented group than in control group. Conclusion: The results of experiment by mouse embryos showed beneficial effects of GM-CSF as a medium supplement. Furthermore, the addition of GM-CSF significantly increased the expression of LIF and IL-1? in mouse embryos. These results suggest that GM-CSF might be a important molecule in embryo implantation.

The Korean Society of Gastroenterology & SIDDS 2035 : Slide Session ;K-LG-06 : Lower GI Tract ; Inhibition of Sonic Hedgehog Pathway Prevent Colitis- Associated Cancer in Mice

( Napapan Kangwan ),( Eun Hee Kim ),( Yoon Jae Kim ),( Kwang Hyun Ko ),( Chang Il Kwon ),( Pil Won Park ),( Ki Baik Hahm ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Background/aims: Colitis-associated cancer is the one of colorectal cancer that is associated with infi ammatory bowel diseases. Sonic hedgehog (SHH) signaling is essential to normal development of gastrointestinal (GI) tracts and it has been reported that aberrantly activated in GI cancers and regulated cancer stem cells fostering tumorigenesis. We have previously found that colitis-associated cancer can be controlled by anti-infi ammatory intervention and SHH pathway suppression inhibited proliferation of extrahepatic biliary tract cancer. Therefore, the aim of this study was to investigate the SHH pathway contributed to colitis-associated cancer development and the effi - cacy of SHH as preventive agents for colitis-associated cancer. Methods: C57BL/6 mice were induced by treatment with 3 mg/kg azoxymethane(AOM) followed by 2% DSS administration for 7 days. SHh inhibitors were treated by oral gavage and the mice were sacrifi ced at 3 and 16 weeks after AOM injection. Thecerulenin, cyclopamine, and itraconazole were used as SHH inhibitor. IL-6 and TNF-a gene expression were analyzed by RT-PCR. Expression of relative proteins was examined by immunohistochemistry and Western blot. Results: Treatment with SHH inhibitors were restored the length of colon and significantly decreased the number of aberrant crypt foci. In addition, SHH inhibitors were reduced tumor incidence and tumor multiplicity. In tumor tissue, SHH inhibitors not only decreased the infi ammation expression of IL-6, TNF-a, STAT3 and NFκB but also attenuated proliferation, while level of apoptosis markers cleaved caspase 3 was increased. Conclusion: Our results imply that the SHh inhibitor could be an effective strategy to prevent colitis-induced colorectal carcinogenesis through the plausible anti-infi ammatory and anti-tumorigenic actions.

고려홍삼의 수지상세포 활성화 효과

김도순(Do-Soon Kim),박정은(Jueng-Eun Park),서권일(Kwon-Il Seo),고성룡(Sung-Ryong Ko),이종원(Jong-Won Lee),도재호(Jae-Ho Do),이성태(Sung-Tae Yee) 고려인삼학회 2006 Journal of Ginseng Research Vol.30 No.3

본 연구에서는 정관장 홍삼의 물(water) extract, 식용발효 주정 extract 및 홍삼 추출물로부터 분리 제조한 crude saponin을 이용하여 면역반응을 매개하는 수지상세포의 활성효과에 대하여 알아보았다. 그 결과 홍삼시료 중, crude saponin 100 ㎍/㎖을 처리하였을 때 수지상세포의 세포표면분자인 MHC class II, CD40, CD80, CD86의 발현이 증가하였으며, phagocytosis는 감소하였다. 또한 홍삼시료를 처리한 수지상세포와 allogeneic T세포를 함께 배양하였을 때, 홍삼시료의 물 extract, 식용발효주정 extract, crude saponin 모두 allogeneic T세포의 증식반응을 유도하였고, IL-2와 IFN-γ의 생산량을 증가시키는 것을 확인하였다. 또한 CD4? syngeneic T세포와 CD8? syngeneic T세포의 반응에서도 T세포의 증식반응을 높게 유도하였으며, CD4? syngeneic T세포에서 IL-2와 IFN-γ의 생산량을 증가시키고, CD8? syngeneic T세포에서는 IFN-γ 생산량을 증가시키는 것을 확인하였다. 이상의 결과로 crude saponin의 경우 수지상세포의 세포표면 공동자극분자의 발현을 유도하고 성숙을 유도함으로써 T세포의 활성을 증진시키는 것으로 생각되며, 물 extract와 식용발효주정 extract는 crude saponin과는 다른 기작으로 T세포 활성화를 유도하는 것을 알 수 있었다. 따라서 실험에 사용한 홍삼시료, 즉 물 extract, 식용발효주정 extract, crude saponin 모두 수지상세포의 활성을 유도하는 물질로써 암항원 특이적 T세포 활성화를 이용한 항암치료에 이용할 수 있는 가능성이 있다고 사료된다. Ginseng is a medicinal herb widely used in Asian countries. Dendritic cells(DCs) play a pivotal role in the initiation of T cell-mediated immune responses, making them an attractive cellular adjuvant for use in cancer vaccines. In this study, we examined the effects of Red-ginseng(water extract, edible and fermented ethyl alcohol extract, crude saponin) on the DCs phenotypic and functional maturation. Immature DCs were cultured in the presence of GM-CSF and IL-4, and the generated immature DCs were stimulated by water extract, edible and fermented ethyl alcohol extract, crude saponin and LPS, respectively, for 24hours. The expression of surface co-stimulatory molecules, including MHC(major histocompatibility complex) class II, CD40, CD80 and CD86, was increased on DCs that were stimulated with crude saponin, but antigen-uptake capacity was decreased. The antigen-presenting capacity of Red-ginseng extracts-treated DCs as analyzed by allogeneic T cells proliferation and IL-2, IFN-γ production was increased. Furthermore, CD4? and CD8? syngeneic T cell(OVA-specific) proliferation and IFN-γ production was significantly increased. However, CD4? syngeneic T cell secreted higher levels of IL-2 in responding but not CD8? syngeneic T cell. These results indicate the immunomodulatory properties of Red-ginseng extracts, which might be therapeutically useful in the control of cancers and immunodeficient diseases through the up-regulation of DCs maturation.

Reduction of Inflammatory Reaction of Poly(D,L-Lactic-C<i>o</i>-Glycolic Acid) Using Demineralized Bone Particles

Yoon, Sun Jung,Kim, Soon Hee,Ha, Hyun Jung,Ko, Youn Kyung,So, Jung Won,Kim, Moon Suk,Yang, Young Il,Khang, Gilson,Rhee, John M.,Lee, Hai Bang Mary Ann Liebert 2008 Tissue engineering. Part A Vol.14 No.4

<P>Poly(lactide-co-glycolic acid) (PLGA) has been widely applied to tissue engineering as a good biocompatible material because of its biodegradability and nontoxic metabolites, but how the inflammatory reaction of PLGA on the surrounding tissue in vivo is reduced has not been discussed sufficiently. We hypothesized that the cells neighboring the PLGA implant might have an inflammatory response that could be reduced by impregnating demineralized bone particles (DBPs) into the PLGA. We manufactured five different ratios of DBP/PLGA hybrid materials, with each material containing 0, 10, 20, 40, and 80 wt% of DBPs of PLGA. For biocompatibility test, NIH/3T3 mouse fibroblasts were cultured on the DBP/PLGA scaffold for 3 days. The inflammatory potential of PLGA was evaluated using messenger ribonucleic acid expression of tumor necrosis factor alpha (TNF-alpha) and interleukin 1-beta (IL-1beta) on a human acute promyelocytic leukemic cell (HL-60). The in vivo response of DBP/PLGA film was compared with that of PLGA film implanted subcutaneously; the local inflammatory response was observed according to histology. The DBP/PLGA scaffold had no adverse effect on NIH/3T3 initial cell attachment and did not affect cell viability. DBP/PLGA films, especially PLGA films containing 80% DBP, elicited a significantly lower expression of IL-1beta and TNF-alpha from HL-60 cells than PLGA film alone. In vivo, DBP/PLGA film demonstrated a more favorable tissue response profile than PLGA film, with significantly less inflammation and fibrous capsule formation as below only 20% of DBP in PLGA film during implantation. This study shows that application of DBPs reduces the fibrous tissue encapsulation and foreign body giant cell response that commonly occurs at the interface of PLGA.</P>

Anti-inflammatory effect of Apo-9′-fucoxanthinone via inhibition of MAPKs and NF-kB signaling pathway in LPS-stimulated RAW 264.7 macrophages and zebrafish model

Kim, Eun-A,Kim, Seo-Young,Ye, Bo-Ram,Kim, Junseong,Ko, Seok-Chun,Lee, Won Woo,Kim, Kil-Nam,Choi, Il-Whan,Jung, Won-Kyo,Heo, Soo-Jin Elsevier 2018 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.59 No.-

<P><B>Abstract</B></P> <P>In this study, we confirmed the anti-inflammatory effect of Apo-9-fucoxanthinone (AF) in <I>in vitro</I> RAW 264.7 cells and <I>in vivo</I> zebrafish model. In lipopolysaccharide (LPS)-stimulated zebrafish, AF significantly decreased the production of reactive oxygen species (ROS), nitric oxide (NO) and cell death. In addition, the mRNA expression of inducible nitric oxide synthase (iNOS), suppressed cyclooxygenase-2 (COX-2) and an inflammatory cytokines; IL-1β, TNF-α were shown reduction. And AF significantly inhibited NO production and expression of iNOS in LPS-stimulated RAW 264.7 cells. Further, AF suppressed COX-2, prostaglandin E2 (PGE<SUB>2</SUB>), and pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) at 25, 50 and 100 μg/mL, respectively. Further mechanistic studies showed that AF suppressed the nuclear factor-kB (NF-kB) pathway and phosphorylation of mitogen-activated protein kinase (MAPK) pathway molecules such as extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). According to the results, AF can be used and applied as a useful anti-inflammatory agent of nutraceutical or pharmaceutical.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Anti-inflammatory effect of Apo-9-fucoxanthinone in <I>in vitro</I> RAW 264.7 cells and <I>in vivo</I> zebrafish </LI> <LI> Apo-9-fucoxanthinone suppressed NO production through NF-kB and MAPKs pathway. </LI> <LI> In LPS-stimulated zebrafish, Apo-9-fucoxanthinone significantly decreased ROS, NO, cell death and pro-inflammatory cytokines. </LI> <LI> Apo-9-fucoxanthinone can be extremely useful as an effective anti-inflammatory agent. </LI> </UL> </P>

Inhibitory Effect of Chan-Su on the Secretion of PGE2 and NO in LPS-stimulated BV2 Microglial Cells

Kim, Min-Hee,Lyu, Ji-Hyo,Lyu, Sun-Ae,Hong, Sang-Hoon,Kim, Won-Il,Yoon, Hwa-Jung,Ko, Woo-Shin The Physiological Society of Korean Medicine and T 2008 동의생리병리학회지 Vol.22 No.5

본 논문은 오랫동안 민간요법으로 염증치료에 사용되어오던 섬수가 lipopolysaccharide(LPS)-자극된 BV2 소교 세포의 nitric oxide(NO) 분비에 미치는 효과에 대해 연구한 내용이다. 실험 결과 섬수는 세포 생존력에 대한 영향 없이 BV2 소교 세포에서 NO 분비를 억제시켰고, nitric oxide synthase (iNOS) 단백질도 감소시켰다. 또한 섬수는 prostaglandin E2 (PGE2) 생산 및 cyclooxygenase (COX)-2 발현을 저지하였고, proinflammatory cytokines과 ${IkB-\alpha}$감소를 억제시켰다. 따라서 섬수가 $I{\kappa}B-{\alpha}$감소를 억제함으로써 NO 합성을 저해하여 항염증작용을 할 수 있다는 내용이다. Chan-Su (Venenum bufonis) has long been for a variety of other purposes including treatment of inflammation in the folk medicine recipe. Since nitric oxide (NO) is one of the major inflammatory parameters, we first studied the effects of Chan-Su on NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, Chan-Su inhibited the secretion of NO in BV2 microglial cells, without affecting cell viability, The protein level of inducible nitric oxide synthase (iNOS) was decreased by Chan-Su, And Chan-Su also inhibited production of prostaglandin E2 (PGE2) and expression of cyclooxygenase (COX)-2. Proinflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$ and IL-12, were inhibited by Chan-Su in a dose-dependent manner. And Chan-Su inhibited the degradation of ${IkB-\alpha}$, which was considered to be inhibitor of nuclear factor $(NF)-{\kappa}B$, one of a potential transcription factor for the expression of iNOS, COX-2 and proinflammatory cytokines. These results suggest that Chan-Su could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of $I{\kappa}B-{\alpha}$ degradation.