Caffeic acid phenethyl ester inhibits the inflammatory effects of interleukin-1β in human corneal fibroblasts

Yang, Jae-Wook,Jung, Won-Kyo,Lee, Chang-Min,Yea, Sung Su,Choi, Yung Hyun,Kim, Gi-Young,Lee, Dae-Sung,Na, Giyoun,Park, Sae-Gwang,Seo, Su-Kil,Choi, Jung Sik,Lee, Young-Min,Park, Won Sun,Choi, Il-Whan Informa Healthcare USA, Inc. 2014 IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY Vol.36 No.5

<P><I>Context</I>: Expression of various inflammatory mediators in corneal fibroblasts contributes to corneal inflammation.</P><P><I>Objective</I>: The purpose of this study was to assess the possible effects of caffeic acid phenethyl ester (CAPE) on the expression of inflammatory mediators during an inflammatory response in human corneal fibroblasts.</P><P><I>Materials and methods</I>: The levels of interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule-1 (ICAM-1) from IL-1β-exposed human corneal fibroblasts were measured with enzyme-linked immunosorbent assays (ELISA). The regulatory mechanisms of CAPE on cellular signaling pathways were examined using Western blot and electrophoretic mobility shift assays. A functional validation was carried out by evaluating the inhibitory effects of CAPE on neutrophil and monocyte migration <I>in vitro</I>.</P><P><I>Results</I>: CAPE inhibited the expression of IL-6, MCP-1 and ICAM-1 induced by the pro-inflammatory cytokine IL-1β in corneal fibroblasts. The activation of AKT and NF-κB by IL-1β was markedly inhibited by CAPE, whereas the activity of mitogen-activated protein kinases (MAPKs) was not affected. CAPE significantly suppressed the IL-1β-induced migration of differentiated (d)HL-60 and THP-1 cells.</P><P><I>Discussion</I>: These anti-inflammatory effects of CAPE may be expected to inhibit the infiltration of leukocytes into the corneal stroma <I>in vivo</I>.</P>

Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells.

Jang, Byeong-Churl,Lim, Ki-Jo,Choi, In-Hak,Suh, Min-Ho,Park, Jong-Gu,Mun, Kyo-Chul,Bae, Jae-Hoon,Shin, Dong-Hoon,Suh, Seong-Il D.A. Spandidos 2007 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.19 No.5

<P>The immunosuppressive effect of triptolide has been associated with suppression of T-cell activation. However, the immunosuppressive effects of triptolide on innate immunity in the epithelial barrier remain to be elucidated. Human beta-defensin (HBD)-2 is an inducible antimicrobial peptide and plays an important role in the innate immunity. We have previously demonstrated that IL-1beta induced HBD-2 mRNA expression in A549 cells through activation of nuclear factor-kappaB (NF-kappaB) transcriptional factor as well as p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK), or phosphatidylinositol-3-kinase (PI3K). In this study, we investigated effects of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells. Triptolide inhibited IL-1beta-induced HBD-2 mRNA expression in a dose-dependent manner. Addition of triptolide did not suppress activation of p38 MAPK, JNK, or PI3K in response to IL-1beta. Triptolide inhibited IL-1beta-induced MAPK phosphatase-1 expression at the transcriptional level and resulted in sustained phosphorylation of JNK or p38 MAPK, explaining the little effect of triptolide on IL-1beta-induced phosphorylation of these kinases. Although triptolide partially suppressed IL-1beta-mediated degradation of IkappaB-alpha and nuclear translocation of p65 NF-kappaB, triptolide potently inhibited NF-kappaB promoter-driven luciferase activity in A549 cells. These results collectively suggest that the inhibitory effect of triptolide on IL-1beta-induced HBD-2 mRNA expression in A549 cells seems to be at least in part mediated through nuclear inhibition of NF-kappaB transcriptional activity, but not inhibition of p38 MAPK, JNK, or PI3K. This inhibition may explain the ability of triptolide to diminish innate immune response.</P>

북강활 에틸아세테이트분획의 비만세포에서의 염증반응 억제효과

서운교 ( Un Kyo Seo ),이주일 ( Ju Il Lee ),박준홍 ( Jun Hong Park ),박용기 ( Yong Ki Park ) 대한본초학회 2008 大韓本草學會誌 Vol.23 No.4

Objectives: In this study, the pharmacological effects of the ethylacetate extract of Ostericum koreanum(North Kangwhal; NK) on allergic inflammation were investigated in activated human mast cells. Methods: North Kangwhal was extracted with 80% methanol for 24 h, and then fractionated with ethylacetate(NK-EtOAc extract). HMC-1 cells, an human mast line, were pre-incubated with different concentrations of NK-EtOAc extract for 30 min, and then stimulated with PMA(50 nM/ml) and A23187(1 μM/ml) at indicated times. The cell toxicity was determined by MTT assay. The concentrations of prostaglandin E2(PGE2) and cytokines(TNF-α, IL-8) were measured by enzyme-linked immunosorbant assay. Results: NK-EtOAc extract(10~50 ㎍/ml) significantly inhibited the productions of PGE2, TNF-α and IL-8 in PMA/A23187-stimulated HMC-1 cells without cell toxicity(0~50 ㎍/ml). NK-EtOAc extract also inhibited PMA/A23187-induced phosphorylation of ERK1/2 MAPK and the NF-κB p65 subunit translocation into the nuclear of HMC-1 cells. Conclusions: This study suggests that NK-EtOAc extract may have an anti-inflammatory property through suppressing the production of inflammatory mediators in activated mast cells and its molecular mechanism underlies the blocking of NF-κB pathway.

전침 자극에 의한 오디 괄약근 운동성 변화에 관한 연구

이성구,김명완,김홍자,서동환,이상수,김동일,유교상,주연호,민병일,김지훈 경희대학교 동서의학연구소 2001 東西醫學硏究所 論文集 Vol.2000 No.-

Background/Aims: This study was designed to evaluated the effects of electroacupuncture on the sphincter of Oddi (SO) motility in humans and to correlate the manometric findings with plasma cholecystokinin (CCK) levels. Methods: Eleven patients (M: F= 5: 6) who had various kinds of biliary disorders were enrolled. SO motility was monitored with a conventional low-compliant continuously perfused technique using ERCP (n=9) or percutaneous transhepatic cholangioscope (n=2). After baseline monitoring for phasic wave contractions of SO, electroacupuncture was applied at a specific acupoint, GB 34, in these 11 patients. A nonspecific acupoint 5 cm away from GB 34 was selected as a control. Manometric parameters of SO were also checked in 6 subjects during stimulation of the control acupoint. CCK plasma levels were measured during the time course of electroacupuncture stimulation. Result: All the manometric parameters including the basal pressure of SO, amplitude, frequency and duration of phasic wave contraction of SO were significantly decreased (p< 0.05) during electroacupuncture stimulation. The inhibition of SO contractility was accompanied by increased CCK plasma levels. After removal of electroacupuncture stimulation, restoration of amplitude and duration to basal condition were noted. A tendency towards the return of SO contractility was also observed in basal pressure and frequency. Stimulation of the control acupoint, however, did not affect the SO contractility and plasma CCK levels. Conclusions: Electroacupuncture stimulation of acupoint GB 34 showed reversible inhibition of SO contraction in humans. We speculate that the response of SO to electroacupuncture stimulation may be mediated by some neurohormonal mechanisms including CCK release. (Korean Journal of Gastrointestinal Motility 2000;6:44-41)

Effects of <i>Ecklonia cava</i> ethanolic extracts on airway hyperresponsiveness and inflammation in a murine asthma model: Role of suppressor of cytokine signaling

Kim, Se-Kwon,Lee, Da-Young,Jung, Won-Kyo,Kim, Ji-Hye,Choi, Inhak,Park, Sae-Gwang,Seo, Su-Kil,Lee, Soo-Woong,Lee, Chang Min,Yea, Sung Su,Choi, Yung Hyun,Choi, Il-Whan Elsevier 2008 BIOMEDICINE AND PHARMACOTHERAPY Vol.62 No.5

<P><B>Abstract</B></P><P><I>Ecklonia cava</I> (EC) is a brown alga that evidences radical scavenging activity, bactericidal activity, tyrosinase inhibitory activity, and protease inhibitory activity. However, its anti-allergic effects remain poorly understood. In the current study, we attempted to determine whether pretreatment with EC induces a significant inhibition of asthmatic reactions in a mouse asthma model. Mice sensitized and challenged with ovalbumin (OVA) evidenced typical asthmatic reactions, as follows: an increase in the number of eosinophils in bronchoalveolar lavage fluid; a marked influx of inflammatory cells into the lung around blood vessels and airways, and airway luminal narrowing; the development of airway hyperresponsiveness; the detection of tumor necrosis factor-alpha (TNF-α) and Th2 cytokines, including IL-4 and IL-5 in the bronchoalveolar lavage (BAL) fluid; and the detection of allergen-specific immunoglobulin E (IgE) in the serum. However, the administration of EC extract prior to the final airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. We also demonstrated that EC extracts treatment resulted in significant reductions on matrix metalloproteinase-9 (MMP-9) and Suppressor of cytokine signaling-3 (SOCS-3) expression and a reduction in the increased eosinophil peroxidase (EPO) activity. The treatment of animals with EC extracts resulted in a significant reduction in the concentrations of the Th2 cytokine (IL-4 and IL-5) in the airways, without any concomitant increase in the concentration of Th1 cytokines. These findings indicate that EC extracts may prove useful as an adjuvant therapy for allergic airway reactions via the inhibition of the Th2 response. Accordingly, this study may provide evidence that EC extract performs a critical function in the amelioration of the pathogenetic process of asthma in mice.</P>

YCG063 inhibits Pseudomonas aeruginosa LPS-induced inflammation in human retinal pigment epithelial cells through the TLR2-mediated AKT/NF-κB pathway and ROS-independent pathways

PAENG, SUNG HWA,PARK, WON SUN,JUNG, WON-KYO,LEE, DAE-SUNG,KIM, GI-YOUNG,CHOI, YUNG HYUN,SEO, SU-KIL,JANG, WON HEE,CHOI, JUNG SIK,LEE, YOUNG-MIN,PARK, SAEGWANG,CHOI, IL-WHAN UNKNOWN 2015 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.36 No.3

<P>YCG063 is known as an inhibitor of reactive oxygen species?(ROS); however, its intracellular mechanisms of action remain poorly understood. In the present study, we investigated the effects of YCG063 on the inflammatory response of Pseudomonas aeruginosa lipopolysaccharide?(PA-LPS)?stimulated human retinal pigment epithelial cells?(RPE cells). Human adult RPE cells?(ARPE?19) were stimulated with PA-LPS. We then investigated the LPS-induced expression of several inflammatory mediators, such as interleukin?(IL)-6, IL-8, monocyte chemoattractant protein-1?(MCP-1) and intracellular adhesion molecule-1?(ICAM-1) in the ARPE-19 cells. We performed an enzyme-linked immunosorbent assay?(ELISA), western blot analysis, electrophoretic mobility shift assay?(EMSA) and fluorescence-activated cell sorting?(FACS) to elucidate the mechanisms involved in the anti-inflammatory effects of YCG063 in the PA-LPS-stimulated cells. The results revealed that treatment with YCG063 significantly inhibited the levels of IL-6, IL-8, MCP-1 and ICAM-1 in the PA-LPS-stimulated ARPE-19 cells. YCG063 also markedly inhibited the phosphorylation of AKT in the PA?LPS-stimulated cells. In addition, the activation of nuclear factor-κB?(NF-κB) was also attenuated folllowing treatment with YCG063. ROS were not generated in the PA-LPS-stimulated cells. In conclusion, our data indicate that YCG063 may prove to be a potential protective agent against inflammation, possibly through the downregulation of Toll?like receptor?2?(TLR2) and the AKT-dependent NF-κB activation pathway in PA-LPS-stimulated ARPE-19 cells. Furthermore, this anti-inflammatory activity occurred through ROS-independent signaling pathways.</P>

Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells

Cho, Mi Suk,Park, Won Sun,Jung, Won-Kyo,Qian, Zhong-ji,Lee, Dae-Sung,Choi, Jung-Sik,Lee, Da-Young,Park, Sae-Gwang,Seo, Su-Kil,Kim, Hak-Ju,Won, Jun Yeon,Yu, Byeng Chul,Choi, Il-Whan Informa Healthcare USA, Inc. 2014 PHARMACEUTICAL BIOLOGY Vol.52 No.7

<P><I>Context</I>: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown.</P><P><I>Objective</I>: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells <I>in vitro</I>.</P><P><I>Materials and methods</I>: To investigate the bioactive potential of CAPE (10 or 20 µM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24 h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used.</P><P><I>Results</I>: CAPE (10 mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20 µM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83 pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713 pg/ml, IC<SUB>50</SUB> = 6.67 µM), IL-6 (4771.5 versus 449.1 pg/ml, IC<SUB>50</SUB> = 5.25 µM), and IL-8 (5991.7 versus 2213.1 pg/ml, IC<SUB>50</SUB> = 9.95 µM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation.</P><P><I>Discussion and conclusion</I>: Our results indicated that CAPE can modulate mast cell-mediated allergic disease.</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>

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>

네트워크 취약점 검색공격에 관한 분석

유일선,최승교 三陟大學校 産業科學技術硏究所 2004 産業科學技術硏究論文集 Vol.9 No.1

Today, the number of automated network vulnerability scanners such as mscan, sscan and nmap is constantly increasing and more attacks are successfully initiated. Thus, such tools cause intrusions and other attacks to become more widespread and sophisticated. This paper analyzes network vulnerability scan attacks and discusses the way of detecting such attacks.