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.

Anti-inflammatory Activity of an Ethanol Extract of Caesalpinia sappan L. in LPS-induced RAW 264.7 Cells

Il Yun Jeong,Chang Hyun Jin,Yong Dae Park,Hyo Jung Lee,Dae Seong Choi,Myung Woo Byun,Yeung Ji Kim 한국식품영양과학회 2008 Preventive Nutrition and Food Science Vol.13 No.4

The anti-inflammatory activities of an ethanol extract of Caesalpinia sappan L. (CS) were investigated in LPS-induced RAW 264.7 cells. Result indicated that CS inhibited the LPS-induced NO production in a dose-dependent manner with an IC?? of 10.9 ㎍/mL. In addition, CS attenuated the iNOS mRNA and protein expression by inhibiting NF-κB activation. CS also suppressed the productions of IL-6 and MCP-1 in a dose-dependent manner, with IC?? values of 15.9 ㎍/mL and 5.47 ㎍/mL, respectively. In addition to the anti-inflammatory activities, CS decreased intracellular ROS formation in the same cells. In conclusion, CS inhibited the production of NO, IL-6 and MCP-1 via a suppression of the NF-κB activation and intracellular ROS generation.

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>

Anti-inflammatory Activity of an Ethanol Extract of Caesalpinia sappan L. in LPS-induced RAW 264.7 Cells

Jeong, Il-Yun,Jin, Chang-Hyun,Park, Yong-Dae,Lee, Hyo-Jung,Choi, Dae-Seong,Byun, Myung-Woo,Kim, Yeung-Ji The Korean Society of Food Science and Nutrition 2008 Preventive Nutrition and Food Science Vol.13 No.4

The anti-inflammatory activities of an ethanol extract of Caesalpinia sappan L. (CS) were investigated in LPS-induced RAW 264.7 cells. Result indicated that CS inhibited the LPS-induced NO production in a dose-dependent manner with an $IC_{50}$ of $10.9\;{\mu}g/mL$. In addition, CS attenuated the iNOS mRNA and protein expression by inhibiting NF-${\kappa}B$ activation. CS also suppressed the productions of IL-6 and MCP-1 in a dose-dependent manner, with $IC_{50}$ values of $15.9\;{\mu}g/mL$ and $5.47\;{\mu}g/mL$, respectively. In addition to the anti-inflammatory activities, CS decreased intracellular ROS formation in the same cells. In conclusion, CS inhibited the production of NO, IL-6 and MCP-1 via a suppression of the NF-${\kappa}B$ activation and intracellular ROS generation.

Ampelopsis japonica Makino extract (AE) inhibits the inflammatory reaction induced by pathogen-associated molecular patterns (PAMPs) in epidermal keratinocytes

( Mi Ra Choi ),( Jin Hyup Lee ),( Dae Kyoung Choi ),( Dong Il Kim ),( Hae Eul Lee ),( Myung Im ),( Young Lee ),( Chang Deok Kim ),( Young Joon Seo ),( Jeung Hoon Lee ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Keratinocytes are the major cells inepidermis, providing barrier components such as cornified cells through the sophisticated differentiation process. In addition, keratinocytes exerts their role as the defense cells via activation of innate immunity. It has been knownthat pathogen-associated molecular patterns (PAMPs) including double-strand RNA and nucleotides can provoke inflammatory reaction in keratinocytes. Objectives: The aim of this study is to evaluate the effect of Ampelopsis japonica Makino extract (AE) on PAMPs-induced inflammatory reaction of keratinocytes. Methods: The effects of AE were determined using poly(I:C)-induced inflammation and imiquimod-induced psoriasiform dermatitis models. Results: In cultured keratinocytes, AE significantly inhibited poly(I:C)-induced expression of inflammatory cytokines, such as IL-1モ, IL-6, IL-8 and TNF-メ. AE significantly inhibited poly(I:C)-induced release of caspase-1 active form (p20), and down-regulated NF-リB signaling pathway. In imiquimod-induced psoriasiform dermatitis model, topical application of AE resulted in significant reduction of epidermal hyperplasia. Conclusion: These results suggest that AE may be a potential candidate for the treatment of skin inflammation.

Ampelopsis japonica Makino Extract Inhibits the Inflammatory Reaction Induced by Pathogen-Associated Molecular Patterns in Epidermal Keratinocytes

( Mi Ra Choi ),( Dae Kyoung Choi ),( Ki Duck Kim ),( Sue Jeong Kim ),( Dong Il Kim ),( Myung Im ),( Young Lee ),( Young Joon Seo ),( Chang Deok Kim ),( Jeung Hoon Lee ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.3

Background: Keratinocytes are the major cells in epidermis, providing barrier components such as cornified cells through the sophisticated differentiation process. In addition, keratinocytes exerts their role as the defense cells via activation of innate immunity. It has been known that pathogen-associated molecular patterns (PAMPs) including double-strand RNA and nucleotides can provoke inflammatory reaction in keratinocytes. Objective: The aim of this study is to evaluate the effect of Ampelopsis japonica Makino extract (AE) on PAMPs-induced inflammatory reaction of keratinocytes. Methods: The effects of AE were determined using poly (I:C)-induced inflammation and imiquimod-induced psoriasiform dermatitis models. Results: In cultured keratinocytes, AE significantly inhibited poly(I:C)-induced expression of inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor-α. AE significantly inhibited poly(I:C)-induced release of caspase-1 active form (p20), and down-regulated nuclear factor-κB signaling pathway. In imiquimod- induced psoriasiform dermatitis model, topical application of AE resulted in significant reduction of epidermal hyperplasia. Conclusion: These results suggest that AE may be a potential candidate for the treatment of skin inflam-mation. (Ann Dermatol 28(3) 352∼359, 2016)

태반 영양모세포주의 혈관내피성장인자 분비에 미치는 Th1형 사이토카인들의 영향

정인배(In Bai Chung),최선주(Sun Ju Choi),홍민(Min Hong),최현일(Hyun Il Choi),이영심(Young Sim Lee),고춘명(Choon Myung Koh),박주영(Joo Young Park) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.5

N/A Embryo implantation and development are critically dependent upon the regulation of angiogenesis and adequate immunologic acceptance. These local angiogenesis and vascular permeability are regulated by the interaction between fetal trophoblast, uterine decidua, and endothelial cells through the key mediator, vascular endothelial growth factor (VEGF). Problem : The mechanism through which VEGF regulation occurs at the feto-maternal interface is poorly understood. The Th1 type cytokines are known to be harmful to the successful maintenance of early pregnancy at the feto-maternal interface. Objective : To clarify whether the Th1 type cytokines could be involved in the regulation of VEGF secretion at the feto-maternal interface. Method of Study : we investigated the effects of Th1 type cytokines on VEGF secretion in human first trimester trophoblast cell-line by using reverse transcription polymerase chain reaction(RT-PCR)and enzyme-linked immunosorbent assay (ELISA). Results : The trophoblast cells expressed VEGF constitutively and the main isoforms were VEGF121 and VEGF165. When cultured in the presence of IFN-γ or IL-2, VEGF secretion was most significantly increased by IFN-γ treatment but not affected by IL-2 treatment. The level of intracellular VEGF was also increased by IFN-γ treatment. Conclusion : These results suggest that IFN-γ, despite of harmful Th1 type cytokine to the maintenance of early pregnancy, may regulate the production of VEGF in early gestational trophoblasts.

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.

급속응고된 Al-Zr 합금의 시효현상에 미치는 Si첨가의 영향

최상욱,박홍일,김명호 울산대학교 1987 연구논문집 Vol.18 No.2

본 연구에서는 급속응고된 Al-Zr 합금의 과포화 고용도에 미치는 제3첨가 원소 Si의 영향 및 급속응고된 Al-Zr-Si 합금계의 시효특성에 관하여 실험적으로 조사하였다. Twin-roller 장치에 의하여 급속응고시킨 시편의 응고속도는 10?? K/s 정도였으며, 이때 Al기지내에 Zr은 약 1 wt.% 정도만이 과포화 고용되었다. 그러나 Si의 첨가량이 증가됨에 따라 Zr의 과포화 고용도는 증대되어 Si의 첨가량이 1 wt.% 일때 Zr은 1.7 wt.% 정도 Al기지내에 완전 과포화 고용되었다. 그리고 Si의 첨가량이 증가됨에 따라 Al-Zr 합금의 미소경도는 증대되었다. Al -1.7wt.%Zr -1.0wt.%Si 합금을 시효처리하면 Si이 우선 미세한 구상석출물을 형성하며 초기 시효경화를 일으킨 후, 잇따라 Zr의 준안정 석출물이 불연속 석출되어 성장하며 최대 시효경화를 나타냄을 알 수 있었다. An experimental investigation has been made about the effects of the third alloying element silicon on the sold solubility of zirconium in the aluminium, and on the ageing phenomena of Al-Zr-Si alloys. Rapidly solidified specimens were prepared by a twin-roller quenching apparatus in the form of long, thin ribbon, whose cooling rate was estimated to be about 10?? K/s. Under such a cooling rate, the maximum solubility of zirconium in solid aluminum was extended to about 1.0wt.%. However, it was extended up to 1.7wt.% by addition of 1.0wt.% silicon. With the increase of silicon content, the microhardness of Al-Zr alloys were increased as well. Ageing of supersaturated Al-1.7wt.% Zr-1.0wt.% Si solid solution appeared to occur in three sequential stages; Ⅰ. precipitation of silicon as fine spherical particles which harden the alloys, followed by Ⅱ. discontinuous precipitation of metastable zirconium phases which produce remarkable age hardening of the alloys, and finally Ⅲ. formation of coarse equilibrium zirconium phases.

악성 질환에서의 고용량 화학요법과 자가말초혈액 조혈모세포이식술 : 단일기관 치료 경험

최정혜,안명주,오호석,이웅수,오석중,이영열,최일영,김인순 대한조혈모세포이식학회 2003 대한조혈모세포이식학회지 Vol.8 No.2

연구배경: 고용량 화학요법은 항암제의 투여 용량에 따라 항암효과가 비례하는 용량반응 관계가 있는 악성종양에서 효과를 기대할 수 있으며 현재 급성백혈병, 악성림프종, 다발성골수종 등의 혈액 종양과 유방암, 고환암, 난소암, 신경아세포종 등의 고형암 환자에서 시행되고 있다. 저자들은 고용량화학요법에 이어 자가조혈모세포이식을 시행 받은 악성 종양 환자를 대상으로 치료효과 및 부작용 등의 임상상을 알아보고자 하였다. 방법: 1997년부터 2003년까지 한양대학교 병원에서 자가조혈모세포이식을 시행 받은 악성 종양 환자 31예(남서 : 여성 15 : 16, 중앙연령: 50세, 다발성골수종 14예, 비호지킨림프종 9예, 유방암 4예, 호지킨림프종 3예, 급성골수성백혈병 1예)를 대상으로 후향적 분석을 시행하였다. 결과: 채집된 단핵구의 중앙값은 5.1×10^(8)/kg (범위 1.6~189.3)이었고 CD34양성세포수의 중앙값은 12.0×10^(6)/kg (범위 1.3~75.1)이었다. 말초혈액 과립구가 500/μL 에 도달하는 중앙값은 11일(범위 8~27)이었고 혈소판이 20,000/μL에 도달하는 중앙값은 11일(범위 0~32)이었다. 고용량 항암화학요법 후 21예가 완전관해, 5예가 부분관해에 도달하였다. 생존한 환자의 중앙추적기간은 29.5개월이었고 전체 환자의 2년 무병생존기간은 55.7%이었고 중앙값은 48.2개월이었다. 2년 생존기간은 62.9%이었으며 중앙값에는 도달하지 않았다. 10예의 사망환자 중 7예가 질병의 진행으로 사망하였고, 조기사망 3예(심부전과 신부전 1예, 장파열 1예, 패혈증 1예)가 있었다. 결론: 이 연구는 포함된 환자의 수가 적고 추적기간이 짧은 단점이 있으나, 다발성골수종, 악성림프종 등의 악성 질환에서 고용량 항암화학요법과 자가조혈모세포이식은 안전하고 효과적인 치료임을 추정할 수 있었다. Background: We performed the current study to evaluate the safety and efficacy of high-dose chemotherapy (HDC) with autologous peripheral blood stem cell transplantation (ASCT) in malignant diseases. Methods: Between January 1997 and March 2003, 31 patients (14 multiple myeloma, 9 Non-Hodgkin's lymphoma, 3 Hodgkin's disease, 4 breast cancer, and 1 acute myelogenous leukemia) underwent HDC with ASCT. Stem cells were collected by CS-3000 after mobilization treatment with chemotherapy and granulocyte colony-stimulating factor. The conditioning regimens included high-dose melphalan, BEAM (BCNU, etoposide, cytosine arabinoside, melphalan), BEAC (BCNU, etoposide, cytosine arabinoside, cyclophosphamide), CPB (cyclophosphamide, cisplatin, BCNU) and others. Results: There were 15 male and 16 female patients and median age was 50 years (range: 29~77). The median number of mononuclear and CD34+ cells was 5.1×10^(8)/kg (1.6~189.3) and 12.0×10^(6)/kg (1.3~75.1), respectively. The median time of neutrophil (>500/μL) and platelet (>20,000/μL) engraftment was 11 (8~27) and 11 (0~32) days after ASCT, respectively. Twenty-two patients experienced neutropenic fever. Twenty-one patients achieved complete remission and 5 patients achieved partial remission after HDC with ASCT. The median follow-up duration for surviving patients was 29.5 months. Causes of death included disease progression (7), sepsis (1), bowel perforation (1), and renal failure (1). Median progression free survival (PFS) was 48.2 months and median overall survival (OS) was not reached. Two-year PFS and OS was 55.7% and 62.9%, respectively. Conclusion: Our results suggest that HDC with ASCT was safe and effective modality in patients with various malignant diseases.