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.

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.

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

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.

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>

Case Reports : Appearance of Psoriasis after Tumor Necrosis Factor-α Blocker and Use of Ustekinumab or Tocilizumab for Refractory Monoarthritis

( Jinyoung Moon ),( Nakwon Kwak ),( Jin Lim ),( Dong Jin Go ),( Jae Hyun Lee ),( Jin Kyun Park ),( Eun Bong Lee ),( Yeong Wook Song ),( Jai Il Youn ),( Eun Young Lee ) 대한류마티스학회 2015 대한류마티스학회지 Vol.22 No.4

Nowadays, tumor necrosis factor-α (TNF-α) blockers are used for treatment of rheumatoid arthritis, inflammatory bowel diseases, ankylosing spondylitis, psoriatic arthritis, and psoriasis. Paradoxically, there are some reports on the appearance of psoriasis after administration of TNF-α blockers. Here, we report on a patient with monoarthritis in a knee joint who experienced psoriasis after TNF-α blocker therapy (adalimumab and etanercept). Oral medication was not a treatment option due to patient intolerance; thus, we tried ustekinumab, an anti-interleukin (IL)-12/23 monoclonal antibody used for treatment of psoriasis. Following ustekinumab injection, psoriatic skin lesions and joint symptoms were much improved. However, in the following period, joint pain and swelling became aggravated and synovial fluid cytokine levels including IL-6 and IL-17 were elevated. The treatment was changed to tocilizumab, a humanized monoclonal antibody against IL-6 receptor. After injection, knee joint swelling rapidly subsided without worsening of psoriatic skin lesions. (J Rheum Dis 2015;22:263-268)

Poster Session : PS 0694 ; Rheumatology ; Appearance of Psoriasis after TNF-a Blocker and Use of Ustekinumab or Tocilizumab for Refractory Monoarthritis

( Jin Young Moon ),( Dong Jin Go ),( Jae Hyun Lee ),( Jin Kyun Park ),( Eun Bong Lee ),( Yeong Wook Song ),( Jai Il Youn ),( Eun Young Lee ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Nowadays, tumor necrosis factor-a (TNF-a) blockers are used for the treatment of RA, infi ammatory bowel diseases (IBD), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis. Paradoxically, there are some reports of appearance of psoriasis after TNF-a blockers. We report a patient who have seronegative mono-rheumatoid arthritis (mono-RA) on knee joint that experienced psoriasis after TNF-a blocker therapy (adalimumab and etanercept). For the patient, oral medication is not available due to intolerance; thus, we tried ustekinumab which is an anti-IL-12/23 monoclonal antibody that has been used to treat psoriasis. After ustekinumab injection, psoriatic skin lesions and joint symptoms were much improved in the patient. But in the following period, joint pain and swelling aggravated and synovial fi uid cytokine levels such as IL-6 and IL-17 were elevated. Treatment was changed to tocilizumab, humanized monoclonal antibody against IL-6 receptor. After injection, knee joint swelling rapidly subsided without worsening of psoriatic skin lesion.

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.

The Nature of Lipopolysaccharide-triggered Nonparenchymal Liver Cell Supernatant Inhabiting Hepatocyte Protein Synthesis in Rats

Park, Il Young,Lee, Jae Hak,Chang, Suk Kyun CATHOLIC MEDICAL CENTER 1988 Bulletin of the Clinical Research Institute Vol.16/17 No.1

Several investigators reported that lipopolysaccharide stimulated nonparenchymal cells can inhibit hepatocyte protein synthesis in vitro and the etiologic mechanism of hepatic failure in multiple organ failure with trauma or sepsis is monocyte-macrophage mediated cell injury. The nature of macrophage or leukocyte secretory products were thought to be oxygen radical, lysozomal enzyme, hydrogen peroxide , neutral pretense or prostaglandin, interleukin 1. Authors investigated to find out the nature of lipopolysaccharide (LPS)-triggered nonparen-chyrnal liver cells (NPC) culture supernatant which can inhibit hepatocyte protein synthesis. 1. Inhibition of hepatoocyte protein synthesis and thymocyte activity was significantly increased in 24 supernatant. Although the duration of exposure was short or long, inhibition of protein synthsis and thymocyte activity were decreased. The thymocyte proliferation by LPS-triggered NPC supernatant were relatively proportional with the degree of inhibition of hepatocyte protein synthesis. 2. Hepatocyte protein synthesis was slight inhibited by commercial Interleukin-1 (IL-1) 50 units and 25 units but not in 10 units or 1 unit. 3. Release of H_2O_2 from LPS-triggered NPC was lower than standard spectrometry of H_2O_2. Then H_2O_2 was not released during incubation period. 4. Lymphocyte proliferation on LPS-triggered NPC supernatant for 24 supernatant were similar to ^3HTdr incorporation of thymocyte by IL-1 1 unit, 5 units and 10 units. The IL-2 content of LPS-triggered NPC supernatant for 24 hours were similar to thymocyte proliferation by IL-1 1 unit, 5 units and 10 units at 12.5%, 25%, 50% of supernatant concentration.