Positive and negative roles of interleukin-6 in bone metabolism , inflammation and cell differentiation : application in oriental medical research

Lee, Dong Kyu,Kang, Dong Hwi,Kim, Dong Il,Lee, Tae Kyun,Park, Young Guk,Kim, Cheorl Ho 대한한의학회 부인과학회 2000 大韓韓方婦人科學會誌 Vol.13 No.2

Interleukin 6 (IL-6)은 여러종류의 세포에서 분화 및 주화인자로 작용하는 사이토카인이다. 사람 IL-6의 분자구조는 21에서 28 kDa의 분자량을 갖는 하나의 폴리펩타이드 단백질로서 N-형과 O-형당부가반응과 세린잔기에 인산화를 수반하여 수식되어 있다. 이 사이토카인은 수성의 28-아미노산 자기로 구성된 시그날배열을 가진 212 아미노산의 전구체 단백질로서 생합성된다. IL-6와 가장 밀접한 분자구조를 갖는 물질로는 granulocyte colony-stimulating factor (G-CSF)가 있으며 사람 IL-6의 유전자는 염색체 7p21에 암호화되어 있다. IL-6는 IL-6수용체 (80 kDa subunit, IL-6Ra)의 a-사슬의 세포의 영역과 상호작용을 거쳐 세포표면에 결합하게 되며 이렇게 생성된 결합체는 gp130수용체와 상호작용하며, 이때 gp130 subunit는 JAK/STAT signaling cascade의 계속적인 활성화능력을 보유하도록 리간드-의존적인 2량화 형성이 유도된다. IL-6Ra의 세포내 영역도메인은 신호전달반응에 아무런 역할을 하지 않으며 IL-6Ra의 세포막통과와 세포질도메인이 결여된 수용성 IL-6수용체도 마찬가지로 IL-6와 반웅하며 상승제로서 가능을 하게 된다. 이러한 광범위한 발현과 효과 때문에 IL-6생성의 생체내에서의 부적절한 발현과 조절은 중요한 생리적인 변화를 야기시킨다. 본 총설에서는 생리적이고 병태생리적인 조건에서의 IL-6의 역할과 기능을 검토하였으며 한의학에서의 면역, 천식, 골대사, 당뇨, 암, 순환기계질환, 신경계질환의 약물개발과 기전해석의 수단으로서 검토하였다. Interleukin 6 (IL-6) is a cytokine that functions as a trophic and differentiating factor in cells of many types. Human IL-6 is a single-chain protein with a molecular mass ranging from 21 to 28 kDa. IL-6 is modified by N- and O-glycosylations, as well as by phosphorylation on serine residues. The cytokine is synthesized as a precursor protein of 212 amino acids with a hydrophobic 28-residue signal sequence. Its closest homolog is granulocyte colony-stimulating factor (G-CSF). The gene for human IL-6 is located on chromosome 7p21. IL-6 binds to the cell surface via an interaction with the extracellular region of the a-chain of the IL-6 receptor (80 kDa subunit, IL-6Ra). This complex then associates with the gp130 receptor. The gpl30 subunit undergoes ligand-dependent dimerization with subsequent activation of the JAK/STAT signaling cascade. The intracellular domain of IL-6Ra does not play a role in signal transduction. The soluble IL-6 receptor, which lacks the transmembrane and cytoplasmic domain of IL-6Ra, is also responsive to IL-6 and acts as an agonist. Because of its wide-ranging expression and effects, the inappropriate expression and modulation of IL-6 production has important physiological consequences. Presently, it was examined that role of IL-6 under physiological and pathophysiological conditions, and its feasibility as a drug discovery target are meaningful in fields of oriental medical research.

위상피세포에서 Helicobacter pylori 형태 변화가 Interleukin-8 분비에 미치는 영향

이학성,김혜원,홍원선,민영일,정훈용,김해련,양석균,이미화 대한소화기학회 1999 대한소화기학회지 Vol.33 No.6

Background/Aims: Interleukin-8 (IL-8) has been reported to play a critical role in Helicobacter pylori (H. pylori)-associated gastric mucosal damage. H. pylori exist in both bacillary and coccoid forms in the stomach. In contrast to bacillary forms, it is not clear whether coccoid forms stimulate gastric epithelial cells to produce IL-8. This study was conducted to investigate the effects of coccoid forms on IL-8 production. Methods: H. pylori strains of ATCC 43504, ATCC 43526 and three clinical isolates were used in the present study. Coccoid forms were induced by culturing bacillary forms of H. pylori for more than 84 hr. After co-culture of two human gastric adenocarcinoma cel lines (KATO III and AGS) with five strains of H. pylori, the levels of IL-8 were determined in th supernatants by enzyme linked immunosorbent assay. Results: The levels of IL-8 in KATO III and AGS cells were markedly elevated up to 6-9 hr after co-culture with the bacillary forms. The IL-8 levels produced in both cell lines by the coccoid forms were significantly lower than those by the bacillary forms in all strains. Conclusions: These results suggest that coccoid forms are much less implicated in IL-8- mediated gastric mucosal damage than bacillary forms.

복막 중피 세포에서 IL-1β 자극에 의한 MCP-1과 RANTES의 생성

송인숙,양원석,이상구,윤견일,박정식,김순배 대한신장학회 2000 대한신장학회잡지 Vol.19 No.5

Recovery of ionic liquid and sugars from hydrolyzed biomass using ion exclusion simulated moving bed chromatography

Mai, Ngoc Lan,Nguyen, Nam Trung,Kim, Jin-Il,Park, Hyuk-Min,Lee, Sung-Kyun,Koo, Yoon-Mo Elsevier 2012 Journal of Chromatography A Vol.1227 No.-

<P><B>Highlights</B></P><P>► Ionic liquid was successfully separated from aqueous sugar mixtures by ion exclusion SMB. ► Ionic liquid and sugar recovery yield depend on the SMB zone flow rates. ► Complete recovery of ionic liquid could be obtained by optimization of SMB zone configuration.</P> <P><B>Abstract</B></P><P>Efficient recovery of ionic liquid (IL) from aqueous mixture of ILs and sugars (which derived from enzymatic or chemical catalyzed hydrolysis of ILs-pretreated biomass) is a major drawback for commercialization of biofuel and platform chemicals production from biomass utilized ILs as pretreatment solvent. In this study, simulated moving bed (SMB) chromatography equipped with ion exclusion column (containing [Emim]<SUP>+</SUP> cation) was investigated to separate sugars (glucose and xylose) which are the main products from biomass hydrolysate and 1-Ethyl-3-methylimidazolium acetate (EmimAc) which is the ILs used for biomass pretreatment. A four-zone SMB system with a configuration of 2-2-2-2 (2 ion exclusion columns in each zone) was used to recover glucose, xylose and EmimAc from their aqueous mixture with yield of 71.38, 99.37 and 98.92%, respectively. Moreover, the optimization of SMB zone configuration by simulation results in a complete recovery of ILs. This result indicates that for the first time, ion exclusion SMB chromatography could be used for complete recovery of ILs from aqueous sugar mixture.</P>

Jahage, Hominis Placenta(HP), suppress bone resorption by inhibition of tyrosine kinase Src, cycloozygenase expression and PGE2 synthesis

양정민,이태균,김동일,Yang, Jeong-Min,Lee, Tae-Kyun,Kim, Dong-Il The Society of Korean Medicine Obstetrics and Gyne 2007 大韓韓方婦人科學會誌 Vol.20 No.4

Purpose: 이 실험은 골다공증의 치료약물로 자하거의 골질재흡수 억제효과를 검토하기 위하여 설계되었다. Methods: 자하거의 골질재흡수 효과를 확인하기 위하여 생쥐의 두개골 골모세포를 이용하여 Cyclooxygenase-1(COX-1), COX-2, $TGF-{\beta}$, $L-1{\beta}$, $TNF-{\alpha}$, IL-6, prostaglandin E2등의 활성화 정도를 측정하였으며, 골조직의 미세구조적 변화를 확인하였다. Results: 자하거는 $IL-1{\beta}$, $TNF-{\alpha}$, IL-6 또는 그 세가지의 조합에 의하여 유발된 PGE2의 생성 뿐만 아니라 COX-2 mRNA 수치도 감소시켰으나 COX-1 mRNA 수치에는 영향을 주지 않았다. 이로써 자하거는 시험관내에서 그리고 생체내에서 펩티드의 인산화를 억제함으로써 골의 재흡수를 저해하였다. 그리고 자하거는 생쥐에서 $IL-1{\beta}$에 의해 유발된 고칼슘혈증을 감소시켰고, 골의 재흡수를 저해하는 경로를 통하여 골에 대한 보호효과를 보여줌으로써 조기에 난소 절제한 쥐에서 골질감소와 미세구조적 변화를 부분적으로 방지하였다. 이러한 결과는 PGE2 생성에 대한 $IL-1{\beta}$, $TNF-{\alpha}$, IL-6사이의 상승효과는 COX-2의 유전자 발현이 증가한 결과이며 이러한 tyrosine kinase가 생쥐의 두개골 골모세포에서 COX-2의 신호전달에 관계한다는 것을 보여준다. Conclusion: 자하거가 생쥐의 두개골 골모세포에서 여러 신호전달물질의 활성화를 통하여 골질재흡수를 저해하는 특성을 확인함으로써 앞으로 골다공증의 예방과 치료에 대한 추가적인 임상연구가 필요할 것으로 사료된다.

생쥐의 B 세포에서 anti-CD40과 rIL-4로 유도된 싸이토카인 생산에 대한 자오가의 효과

성일창 ( Il Chang Sung ),김형환 ( Hyung Hwan Kim ),안덕균 ( Duk Kyun Ahn ),이용섭 ( Yong Sup Lee ),서영배 ( Young Bae Seo ),최호영 ( Ho Young Choi ) 대한본초학회 2003 大韓本草學會誌 Vol.18 No.2

N/A Objectives : In order to study the anti-allegy effect of water extract of Acanthopanacis senticosi Radix (ASR) on the B-cells from healthy Balblc mice. Methods : The cytotoxicity of ASR was measured with the murine normal lung fibroblast cells by modified SRB assay. And the murine splenic B-cells was stimulated with anti-CD40 mAb and rIL4. The various cytokines related with allergy were measured by flow-cytometry and by RT-PCR with electophoresis. Results : The anti-allegy effects to ASR were identified and observed. The cytotoxicity of ASR on mouse lung fibroblast cells showed no significant activities. ASR had inhibitory effect on CD23+, CD69+, and IgE expression by ASR with anti-CD40 mAb plus rL-4-stimulated murine splenic B-cells. ASR had inhibitory effect on cytokines (E-lb, IL-4, IL-6, IL-10, TNF-a, TGF-81, INF-Y) and transcript expression and IgE production by ASR with anti-CD40 mAb plus rIL-4-stimulated murine splenic B-cells. Conclusion : We concluded that ASR showed anti-allegy effect on murine splenic B-cells.

Effects of Carthamus tinctorius L. seed extracts on regulation of cellular proliferation, prostaglandin E₂synthesis and plasminogen activator activity in the mouse calvarial bone cells

Lee,Dong-Young,Bae,Man-Jong,Kim,Dong-Il,Lee,Tac-Kyun,Nam,Kyung-Soo,Lee,Dong-Kyu,Kim,Cheorl-Ho 경산대학교 생명자원개발연구소 2000 생명자원과 산업 Vol.4 No.-

Medicinal extracts of Honghwain (Carthamus tinctorius L. seed) (CTE) was tested for whether they could inhibit IL-1β-induced PGE₂productional. Cell viability was not significaltly affected by treatment with the indicated concentration of the extracts. The CTE extracts were shown to havethe inhibitory effects against the synthesis of PGE₂. we also examined the effect of the pretreatment with a various concentrations of the CTE extracts then treated the PGE₂-induction agents. Pretreatment of the CTE extracts for 1 h, which by itself had little effect on cell survival, did not enhance the synthesis of PGE₂. Furthermore, the CTE extracts were shown to have the the protective effects against plasminogen dependent fibrinolysis induced by the bone resorption agents of IL-1β. Pretreatment of the CTE extracts for 1 h did not enhance the plasminogen dependent fibrinolysis. Finally, calcitonin showed the inhibitory activity the IL-1β-stimulated bone resorption in the mouse calvarial bone cells having both of the osteoblast and osteoclast cells. Seemingly, pretreatment of the CTE extracts for 1 h reduced the bone resorption. These results clearly indicated that calcitonin and CTE extracts play key roles in inhibition of the osteoclast-mediated bone resorption, and also indicated that the CTE-water extracts are highly stable and applicable to clinical uses in osteoporosis.

人蔘이 羊水感染에 의한 早産에 미치는 영향

尹成獻,趙亨來,金瞳一,李泰均,南景琇 대한한의학회 부인과학회 2000 大韓韓方婦人科學會誌 Vol.13 No.2

This study was performed to investigate the effect of Panax ginseng on preterm labor by amniotic infection. The results of this study were as follows; 1. Interleukin-6(IL-6) production induced lipopolysaccharide(LPS) or Interleukin-1β (IL-19) was inhibited by Panax ginseng hot water-extracts. 2. Production of tumor necrosis factor-α (TNT-α) was not inhibited by Panax ginseng on L929 cytotoxicity assay. 3. Phospholipase A_2(PLA_2) induced LPS in WISH cell was inhibited by Panax ginseng, and also induced IL-1β was inhibited low concentration. 4. PGE_2 production induced LPS and IL-1β was inhibited by Panax ginseng hot water-extracts on PGE_2 enzyme immunoassay. 5. Leukotriene C4 (LTC4) production induced LPS and also IL-1β was inhibited by Panax ginseng hot water-extracts. 6. Panax ginseng may be useful for treatment of preterm labor by amniotic infection because it can inhibit inflammation response induced infection.

Preliminary study on the effect of inflamed TMJ synovial fluid on the intracellular calcium concentration and differential expression of iNOS and COX-2 in human immortalized chondrocyte C28/I2

Eun-Ah Choi,Dong-Geun Lee,Chang-Hoon Chae,Young-Il Chang,Young-Ju Park,Young-Kyun Kim 대한구강악안면외과학회 2006 대한구강악안면외과학회지 Vol.32 No.1

Objective. The objective of this study was to examine the hypothesis that inflammatory synovial fluid from TMJ internal derangement initiates a transient increase in intracellular calcium concentration ([Ca2+]i) in chondrocytes and the induced Ca2+ signaling affects iNOS/COX-2 gene expression patterns following exposure to inflamed synovial fluid. Materials and Methods. Two female adult patients with symptoms of TMD who agreed to participate in the study were selected for this study. Immortalized human juvenile costal chondrocyte C-28/I2 was grown to 80% confluency and synovial fluids from two patients were added respectively to culture media for 24 hours at the concentration of 100ng/10ml. Confocal laser scanning microscope (CLSM) was used to examine changes of intracellular calcium concentration ([Ca2+]i). RT-PCR was performed to identify the expression profile of IL-1α, iNOS, COX-2. Results. Increased [Ca2+]i was observed in chondrocytes subjected to inflamed synovial fluid compared to control cultures and in respective cultures exposed to inflamed synovial fluids from each patient, IL-1β, COX-2 mRNA were detected. However, in neither case iNOS mRNA was expressed. IL-1α, COX-2, and iNOS mRNA were expressed in control culture. Conclusion. Our results show that immortalized chondrocytes cultured with inflamed synovial fluids from patients diagnosed as disc displacement without reduction and limitation in mouth opening showed increased calcium concentration and expression of COX-2 while inhibiting the production of iNOS, which in turn could adversely affect the chondrocytes in at least short term by hindering physiologic role of NO against inflammatory cascades. These findings suggest that inflamed synovial fluid may differentially regulate the transcriptomes of relevant inflammatory mediators, especially iNOS/COX-2 axis in chondrocytes through adjusting calcium transients.

Deep resequencing of 131 Crohn's disease associated genes in pooled DNA confirmed three reported variants and identified eight novel variants

Hong, Sung Noh,Park, Changho,Park, Soo Jung,Lee, Chang Kyun,Ye, Byong Duk,Kim, You Sun,Lee, Seungbok,Chae, Jeesoo,Kim, Jong-Il,Kim, Young-Ho BMJ Publishing Group Ltd 2016 Gut Vol.65 No.5

<P>Objective Genome wide association studies (GWAS) and meta-analyses for Crohn's disease (CD) have not fully explained the heritability of CD, suggesting that additional loci are yet to be found and that the known loci may contain high effect rare risk variants that have thus far gone undetected by GWAS. While the cost of deep sequencing remains too high to analyse many samples, targeted sequencing of pooled DNA samples allows the efficient and cost effective capture of all variations in a target region. Design We performed pooled sequencing in 500 Korean CD cases and 1000 controls to evaluate the coding exon and 50 and 30 untranslated regions of 131 CD associated genes. The identified genetic variants were validated using genotyping in an independent set of 500 CD cases and 1000 controls. Results Pooled sequencing identified 30 common/low single nucleotide variants (SNVs) in 12 genes and 3 rare SNVs in 3 genes. Our results confirmed a significant association of CD with the following previously reported risk loci: rs3810936 in TNFSF15 (OR= 1.83, p< 2.2x10(-16)), rs76418789 in IL23R (OR= 0.47, p= 1.14x10(-8)) and rs2241880 in ATG16L1 (OR= 1.30, p= 5.28x10(-6)). In addition, novel loci were identified in TNFSF8 (rs3181374, OR= 1.53, p= 1.03x10(-14)), BTNL2 (rs28362680, OR= 1.47, p= 9.67x10(-11)), HLA-DQA2 (rs3208181, OR= 1.36, p= 4.66x10(-6)), STAT3 (rs1053004, OR= 1.29, p= 2.07x10(-5)), NFKBIA (rs2273650, OR= 0.80, p= 3.93x10(-4)), NKX2-3 (rs888208, OR= 0.82, p= 6.37x10(-4)) and DNAH12 (rs4462937, OR= 1.13, p= 3.17x10(-2)). A novel rare SNV, rs200735402 in CARD9, was shown to have a protective effect (OR= 0.09, p= 5.28x10(-5)). Conclusions Our deep resequencing of 131 CD associated genes confirmed 3 reported risk loci and identified 8 novel risk loci for CD in Koreans, providing new insights into the genetic architecture of CD.</P>