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>

Corrosion and Oxidation Resistance Behaviors of Ta-Containing Low Alloying Zirconium

Il‑Hyun Kim,Yang‑Il Jung,Byoung‑Kwon Choi,Hyun‑Gil Kim,Jae‑Il Jang 대한금속·재료학회 2021 METALS AND MATERIALS International Vol.27 No.8

Zirconium alloys are widely used to fabricate nuclear fuel claddings, and thus is desirable to improve the resistance of suchalloys to corrosion and structural instability. In this study, Ta was used as an alloying element to improve the corrosion andoxidation resistance of zirconium alloys. The model alloy (TaZL) contained 0.03 wt% Ta and other elements with a proportionof less than 1 wt% in total (0.1 wt% Nb, 0.4 wt% Fe, 0.2 wt% Cr) in a zirconium base. The corrosion test involving pressurizedwater at 360 °C and oxidation test involving steam at 1200 °C indicated that TaZL exhibited the lowest weight gains amongthose of compared conventional and advanced Zr alloys. The corrosion and oxidation resistances of TaZL were respectivelyimproved by 4 and 1.5 times compared to the corresponding values of Zircaloy-4. The microstructures of the oxide formedon TaZL were columnar along the oxide growth direction and did not change from columnar to equiaxed, which resulted inthe high resistance of the alloy to corrosion and oxidation.

Effects of the pro-inflammatory milieu on the dedifferentiation of cultured fibroblast-like synoviocytes

CHOI, HONG SEO,RYU, CHUN JEIH,CHOI, HYUN MI,PARK, JIN SUNG,LEE, JAE-HOON,KIM, KANG IL,YANG, HYUNG-IN,YOO, MYUNG CHUL,KIM, KYOUNG SOO D.A. Spandidos 2012 MOLECULAR MEDICINE REPORTS Vol.5 No.4

<P>The aim of this study was to determine whether the inflammatory milieu and/or hypoxia induces the dedifferentiation of synovial cells into mesenchymal stem-like cells, which may contribute to the tumor-like growth of synovial cells. Expression of mesenchymal stem cell markers (CD24, CD44, CD90, CD106, CD146 and Stro-1) was compared among cultured fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), bone marrow mesenchymal stem cells (BM MSCs) and normal dermal fibroblasts. After the cells were stimulated with pro-inflammatory cytokines for 3 days under hypoxia or normoxia, the stem cell markers were analyzed by FACS. CD44 and CD90 were expressed constitutively in all four cell types. Only the BM MSCs strongly expressed CD146. The expression of stem cell markers was similar between FLSs from RA and those from OA patients. In addition, the expression levels in FLSs were similar to those in normal dermal fibroblasts. The stimulation of FLSs and dermal fibroblasts with IL-1β or a mixture of cytokines under hypoxia did not induce a marked change in the expression of stem cell markers. These results indirectly suggest that the pro-inflammatory milieu may be not sufficient to induce the dedifferentiation of FLSs in arthritic joints.</P>

몇 가지 항균제가 시험관내에서 내독소와 TNF-α, IL-6 분비에 미치는 영향

최정현,문건웅,김명훈,이동건,박윤희,김상일,김태연,유진홍,김양리,신완식,강문원 대한화학요법학회 1997 대한화학요법학회지 Vol.15 No.2

To evaluate antibiotic-induced endotoxin release(AIER) and its correlation with some cytokines, we measured endotoxin level and tumor necrosis factor alpha(TNF-α) and interleukin6(IL-6) production in mononuclear cells in vitro after exposure of Pseudomonas aeruginosa to antibiotics belonging to different class with two extreme concentrations. The tested concetration of antibiotics were set up according to peak serum level. The low concetration of ceftazidirne and low concentration of imiperiem increased AIER, but high concentration of ceftazideme, high concentration of ciprofloxacin, high concentration of cefoperazone/sulbactam, high concentration of amikacin, and high concentration of meropenem reduced AIER.Interestingly, combined treatment of these antibiotics markedly reduced AIER, But the major cyotkines, TNF-α and IL-6 were not affect by type and concettration of antibiotics, combined treatment of antibiotics, and level of endotoxin released by antiboitics. In this study, we observed AIER was different according to type of antibiotics, concentration of antibiotics, and combination of antibiotics, But AIER had poor correlation with TNF-α and IL-6 in Pseudomonas aeruginosa. It suggests that cytokine release is not solely dependent to endotoxin, but more complex cascade is needed. More invesfigations, such as endotoxin induced cytokine mRNA expression, relationship with penicillin-binding proteins and endotoxin-neutralizing effect of antibiotic itself, must be performed.

Chronic alcohol consumption induces migration of IL-1R2+ monocytes from the bone marrow into the liver by neuro-immunologic pathway

Young-Ri Shim,Hee-Hoon Kim,Keungmo Yang,Tom Ryu,Kyurae Kim,Sung Eun Choi,Minjeong Kim,Chae-Rin Woo,Young-Sun Lee,Won-Il Jeong 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Liver is challenged by diverse detrimental substances through multiple metabolic processes, but it is less prone to inflammation. In chronic alcohol consumption, although the migration of monocytes from bone marrow (BM) into liver is increased, alcoholic hepatitis rarely occurs. Thus, we investigated the sub-population of liver macrophages showing anti-inflammatory roles through single-cell RNA sequencing (scRNA-Seq) after chronic EtOH-feeding. Interestingly, in scRNA-seq and flow cytometry analyses of hepatic macrophages, the phenotype of Ly6Clow (anti-inflammatory) cells was dramatically altered by ethanol intake. In particular, they were highly expressed interleukin-1 type II receptor (IL-1R2), a decoy receptor of IL-1β. Intriguingly, IL-1R2+ Ly6Clow macrophages showed decreased CX3CR1 expression, which was confirmed not only in the liver, but also BM and blood, suggesting monocytes from BM affected by ethanol might migrate into the liver. We found that the Leptin Receptor+ mesenchymal stromal cells (LepR+ MSCs), which were located around blood vessels expressing CX3CL1 to hold CX3CR1+ macrophages, could express alcohol dehydrogenase to metabolize ethanol in BM. Ethanol metabolism in LepR+ MSCs was induced both production of chemokines (CXCL9 and 10) and the excretion of glutamate via cystine-glutamate anti-porter xCT to recruit and activate the CXCR3+ BM NK cells to produce interferon-γ in a metabotropic glutamate receptor 5 (mGluR5)-dependent manner. Indeed, IFN-γ production was significantly decreased in EtOH-fed mice when we depleted mGluR5 in NK cells. In turn, NK cell-derived IFN-γ down-regulated CX3CR1 expression in BM Ly6Clow monocytes, consequently induced egress of Ly6Clow monocytes into the blood and migration into the liver to suppress alcoholic inflammation. In conclusion, glutamate of LepR+ MSCs imposed egress license on anti-inflammatory IL-1R2+ Ly6Clow monocytes through NK cell-derived IFN-γ-mediated suppression of CX3CR1, suggesting a potential therapeutic inter-organ crosstalk between BM and liver in alcoholic liver disease.

Association of Increased Pulmonary Interleukin-6 with the Priming Effect of Intra-Amniotic Lipopolysaccharide on Hyperoxic Lung Injury in a Rat Model of Bronchopulmonary Dysplasia

Kim, Do-Hyun,Choi, Chang Won,Kim, Ee-Kyung,Kim, Han-Suk,Kim, Beyong Il,Choi, Jung-Hwan,Lee, Myong Jin,Yang, Eun Gyeong S. Karger AG 2010 NEONATOLOGY Vol.98 No.1

<P><I>Background:</I> The authors previously demonstrated the priming effect of intra-amniotic lipopolysaccharide (LPS) on hyperoxic lung injury in a rat model of bronchopulmonary dysplasia (BPD). <I>Objectives:</I> To investigate the mechanism underlying this priming effect by determining biochemical profiles in a rat model of BPD. <I>Methods:</I> The rat model involved intra-amniotic LPS administration and postnatal hyperoxia (85%). The mRNA expressions of <I>interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), basic fibroblast growth factor (bFGF),</I> and <I>transforming growth factor </I>β<SUB><I>1</I></SUB><I> (TGF-</I>β<SUB><I>1</I></SUB><I>),</I> as well as the protein levels of IL-6, VEGF, and protein carbonyl in lung tissue were compared between the LPS plus hyperoxia, the LPS only, the hyperoxia only, and the control groups. <I>Results:</I> Morphometric analysis of lung tissues demonstrated that alveolarization was significantly inhibited only in the LPS plus hyperoxia group. IL-6 protein levels and its mRNA expression in the lungs were significantly increased only in the LPS plus hyperoxia group. Neither LPS nor hyperoxia increased IL-6 in the lungs independently. <I>bFGF</I> mRNA expression was significantly decreased in the LPS-treated groups. VEGF protein levels were significantly reduced by hyperoxia, whereas protein carbonyl levels were increased by intra-amniotic LPS or hyperoxia. No additional significant change to VEGF or protein carbonyl levels was produced by intra-amniotic LPS or hyperoxia. There were no significant differences in the mRNA expressions of <I>VEGF, VEGFR-2,</I> and <I>TGF-</I>β<SUB><I>1</I></SUB>. <I>Conclusions:</I> The priming effect of intra-amniotic LPS on hyperoxic lung injury may be associated with IL-6 elevation in the lungs.</P><P>Copyright © 2009 S. Karger AG, Basel</P>

탈미네랄화 골분(DBP)이 PLGA 지지체의 염증반응을 완화시킨다

최방실 ( Bang Sil Choi ),김순희 ( Soon Hee Kim ),윤선중 ( Sun Jung Yun ),하현정 ( Hyun Jung Ha ),김문석 ( Moon Suk Kim ),양영일 ( Young Il Yang ),손영숙 ( Young Sook Son ),강길선 ( Gil Son Khang ),이종문 ( John M. Rhee ),이해방 ( 한국조직공학과 재생의학회 2006 조직공학과 재생의학 Vol.3 No.3

We developed the demineralized bone particle(DBP) impregnated poly(lactide-co-glycolide)(PLGA) scaffolds(PLGA/DBP) to investigate the effect of adhesion, growth, viability and inflammatory reaction of the cells. PLGA/DBP scaffolds were prepared by solvent casting/salt leaching method and were characterized by porosimeter, and scanning electron microscopy. NIH/3T3 fibroblast cells were cultured in the PLGA/DBP scaffolds as well as film and MTT assay was used to assess the viability of cells. Also, human promyelocytic leukemia cells(HL-60) were cultured in the PLGA/DBP scaffolds. We observed IL-1ß? and TNF-α expression of HL-60 cells seeded in PLGA/DBP scaffold by RT-PCR. NIH/3T3 fibroblast cell seeded on PLGA/DBP film were more adhere and spread with increasing DBP content due to increasing hydrophilicity and bioactivity. The fluorescence intensity of the band of TNF-α and IL-1ß? gene was decreased with increasing the concentration of DBP. It seems that the DBP affected on the improvement of physicochemical properties of PLGA such as biocompatibility, wettability and inflammatory response.

Blockade of Retinol Metabolism Protects T Cell-Induced Hepatitis by Increasing Migration of Regulatory T Cells

Lee, Young-Sun,Yi, Hyon-Seung,Suh, Yang-Gun,Byun, Jin-Seok,Eun, Hyuk Soo,Kim, So Yeon,Seo, Wonhyo,Jeong, Jong-Min,Choi, Won-Mook,Kim, Myung-Ho,Kim, Ji Hoon,Park, Keun-Gyu,Jeong, Won-Il Korean Society for Molecular and Cellular Biology 2015 Molecules and cells Vol.38 No.11

Retinols are metabolized into retinoic acids by alcohol dehydrogenase (ADH) and retinaldehyde dehydrogenase (Raldh). However, their roles have yet to be clarified in hepatitis despite enriched retinols in hepatic stellate cells (HSCs). Therefore, we investigated the effects of retinols on Concanavalin A (Con A)-mediated hepatitis. Con A was injected into wild type (WT), Raldh1 knockout ($Raldh1^{-/-}$), $CCL2^{-/-}$ and $CCR2^{-/-}$ mice. For migration study of regulatory T cells (Tregs), we used in vivo and ex vivo adoptive transfer systems. Blockade of retinol metabolism in mice given 4-methylpyrazole, an inhibitor of ADH, and ablated Raldh1 gene manifested increased migration of Tregs, eventually protected against Con A-mediated hepatitis by decreasing interferon-${\gamma}$ in T cells. Moreover, interferon-${\gamma}$ treatment increased the expression of ADH3 and Raldh1, but it suppressed that of CCL2 and IL-6 in HSCs. However, the expression of CCL2 and IL-6 was inversely increased upon the pharmacologic or genetic ablation of ADH3 and Raldh1 in HSCs. Indeed, IL-6 treatment increased CCR2 expression of Tregs. In migration assay, ablated CCR2 in Tregs showed reduced migration to HSCs. In adoptive transfer of Tregs in vivo and ex vivo, Raldh1-deficient mice showed more increased migration of Tregs than WT mice. Furthermore, inhibited retinol metabolism increased survival rate (75%) compared with that of the controls (25%) in Con A-induced hepatitis. These results suggest that blockade of retinol metabolism protects against acute liver injury by increased Treg migration, and it may represent a novel therapeutic strategy to control T cell-mediated acute hepatitis.

Effects of Aralia cordata Thunb. on Proteoglycan Release, Type II Collagen Degradation and Matrix Metalloproteinase Activity in Rabbit Articular Cartilage Explants

Baek, Yong-Hyeon,Seo, Byung-Kwan,Lee, Jae-Dong,Huh, Jeong-Eun,Yang, Ha-Ru,Cho, Eun-Mi,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk The Korean Acupuncture Moxibustion Medicine Societ 2005 대한침구의학회지 Vol.33 No.4

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

Effects of Aralia cordata Thunb. on Proteoglycan Release, Type II Collagen Degradation and Matrix Metalloproteinase Activity in Rabbit Articular Cartilage Explants

Baek, Yong-Hyeon,Seo, Byung-Kwan,Lee, Jae-Dong,Huh, Jeong-Eun,Yang, Ha-Ru,Cho, Eun-Mi,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk The Korean AcupunctureMoxibustion Medicine Society 2005 대한침구의학회지 Vol.22 No.2

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.