흰쥐 경골의 신연 골형성술에서 염증성 싸이토카인의 발현

황일웅(Il Ung Hwang),조태준(Tae-Joon Cho),최인호(In Ho Choi),정진엽(Chin Youb Chung),유원준(Won Joon Yoo),김은희(Eun Hee Kim) 대한정형외과학회 2004 대한정형외과학회지 Vol.39 No.1

목적: 본 연구의 목적은 신연 골형성술에서의 염증성 싸이토카인의 발현 양상을 일반 골절 치유 과정과 비교하는 것이다. 대상 및 방법: 흰쥐 경골의 단순 골절 치유 모델과 신연 골형성술 모델을 대상으로 3주에 걸쳐서 단계적으로 골 조직을 채취하였다. 총 리보핵산을 추출하고 각종 염증성 싸이토카인 발현의 시간적 변화를 검사하였다. 수술 후 7일과 9일째에 조직에서 면역조직화학 검사를 통해서 IL-6의 공간적 발현 양상을 조사하였다. 결과: IL-1β, IL-6는 단순 골절 치유 과정에서 수술 후 1일째에 발현이 절정에 달하였다가 3일째부터 발현이 감소하여 수술 전 상태로 회복되었다. IL-1β는 신연 골형성술 중 신연 기간에도 발현의 변화가 없었으나 IL-6은 신연을 시작함에 따라 다시 발현이 증가하는 양상을 보였다. 면역조직화학 검사장 IL-6은 골수 세포 뿐 아니라 연골세포, 골모세포 그리고 신연 간격의 미성숙 간엽세포에서 발현이 확인되었다. 결론: 신연 변형력에 의한 IL-6의 발현이 유도되는 것을 확인하였으며, 이는 조절된 염증 반응이 신연 골형성술 과정에서 신생골 형성에 부분적으로 기여할 가능성을 시사하는 것으로 생각된다. Purpose: The purposes of this study were to investigate the expression pattern of pro-inflammatory cytokines during distraction osteogenesis and to compare these with expression during simple fracture healing. Materials and Methods: Regenerated bones from the rat tibia subjected distraction osteogenesis and simple fracture healing models were harvested over three-week periods. Temporal expressions of mRNA of pro-inflammatory cytokines were investigated by RNase protection assay. Immunohistochemical studies for IL-6 were performed in postoperative day 7 and 9 tissue section specimens. Results: IL-1β and IL-6 produced detectable signals, while IL-1α, TNF α and TNF β did not. The mRNA expressions of IL-1β and IL-6 were markedly upregulated on postoperative day 1 and then subsided to the preoperative level. IL-1β mRNA expression remained the same even when distraction began. However, IL-6 mRNA expression was reactivated during the distraction phase. Immunohistochemical study revealed the expressions of IL-6 not only at the transitional zone of the transchondroid ossification, in young osteoblasts lining newly formed trabeculae and in hematopoietic cells in the marrow but also in primitive mesenchymal cells at the distraction gap. Conclusion: Distraction strain re-induced IL-6 expression during distraction osteogenesis, which suggests that well-controlled inflammatory reaction might contribute to active new bone formation in distraction osteogenesis.

IL-$1{\beta}$ 처리 백서 두개관 세포의 mineral trioxide aggregate에 대한 반응

이술현,박지일,김영준,Lee, Sool-Heon,Park, Ji-Il,Kim, Young-Joon 대한치주과학회 2009 Journal of Periodontal & Implant Science Vol.39 No.3

Purpose: The purpose of this study was to investigate the ability of Mineral trioxide aggregate(MTA) to support osteoclastic differentiation from fetal rat calvarial cell. Methods: In this study, response of IL-6, RANKL, and OPG in fetal rat calvarial cells stimulated with IL-$1{\beta}$ on MTA was evaluated by ELISA and RT-PCR. Results: The results were as follows; there was no significant difference between glass and MTA at 5days. In ELISA analysis, Glass group and MTA group showed similar IL-6 expression, Glass+IL-$1{\beta}$ group and MTA+IL-$1{\beta}$ group showed similar IL-6 expression. In RT-PCR analysis, Glass group and MTA group showed similar IL-6, RANKL, OPG mRNA expression, MTA+IL-$1{\beta}$ group and Glass+IL-$1{\beta}$ group showed 3 fold increase of IL-6 and RNAKL mRNA expression when compared with MTA group. All groups showed similar OPG mRNA expression. Conclusions: MTA does not suppress cell proliferation and increase the proinflammatory cytokine that induce osteoclastogenesis. Thus, MTA is biocompatible material that could be used in various clinical conditions.

Chronological changes in inflammatory cytokines immunoreactivities in the mouse hippocampus after systemic administration of high dosage of tetanus toxin.

Yan, Bing Chun,Park, Joon Ha,Kim, In Hye,Shin, Bich Na,Ahn, Ji Hyeon,Yoo, Ki-Yeon,Lee, Deuk-Sik,Kim, Myong Jo,Kang, Il-Jun,Won, Moo-Ho Springer-Verlag 2012 Experimental brain research Vol.223 No.2

<P>Tetanus toxin (TeT) is an exotoxin and has a capacity for neuronal binding and internalization. In the present study, we compared changes in the immunoreactivities and protein levels of interleukin (IL-) 2 as a pro-inflammatory cytokine and IL-4 as an anti-inflammatory cytokine in the hippocampus proper (HP) and dentate gyrus (DG) after systemic treatment of 10 or 100?ng/kg TeT into mice. In this study, we could not find any neuronal damage or loss in any subregions of the hippocampus after TeT treatment. In the control groups, strong IL-2 immunoreactivity was shown in the stratum pyramidal (SP) of the HP and in the granule cell layer (GCL) of the DG. At 6?h post-treatment, IL-2 immunoreactivity was hardly detected in the SP and GCL; however, strong IL-2 immunoreactivity was shown in the stratum oriens of the HP in both the groups. Thereafter, intermediate IL-2 immunoreactivity was shown in the SP and GCL. On the other hand, intermediate IL-4 immunoreactivity was detected in the SP and GCL of the control groups. At 6?h post-treatment, IL-4 immunoreactivity in the SP and GCL was apparently increased. Thereafter, IL-4 immunoreactivity was lower than that at 6?h post-treatment. In brief, IL-2 and 4 immunoreactivities were easily detected in SP and GCL in the controls and dramatically decreased and increased at 6?h post-treatment, respectively.</P>

DBA/1JCrj Mouse에 있어서 콜라젠유도관절염에 관한 면역학적 고찰

박승규,이지연,정일엽,최용경,최인성,김효준 大韓免疫學會 1996 大韓免疫學會誌 Vol.18 No.3

There is growing evidence that a variety of cytokines are secreted by cells at the inflammation sites of rheumatoid arthritis (RA) and that CDS+ B cell, a minor subtype of B cell population producing natural autoantibodies, is implicated in pathogenesis of RA. In this study, we evaluated the both cytokne levels and change of CDS+ B cell population in the peripheral blood from DBA/lJCrj mice(H-2`) which are collagen-induced arthritis(CIA) susceptible strain. Surprisingly, the healthy DBA/1JCrj and MRL/Ipr/Ipr(H-2'`) mice which were autoimmune susceptible strains tested in this experiment, showed lower IL-4, IL-6 and IL-10 levels in serum by 60% than heal-thy normal mouse strains such as Balb/c(H-2d), C57BL/6(H-2') and outbred ICR mice. MRL/lpr/ 1pr mice in which onset of spontaneous autoimmune disease is dependent upon age were similar to healthy DBA/1JCrj mice in levels of the cytokines in the serum when they are young. After the CIA(for DBA/1JCrj) or the spontaneous autoimmune disease(for MRL/lpr/Ipr) had been developed in the susceptible mouse strains, the levels of IL-6 and IL-4 in the serum were increased to 1.8- and 13-fold, respectively, as compaired with those from control groups while level of IL-10 remained relatively constant. The elevated levels of IL-4- and IL-6, however, in the serum from mice with disease status were still below those of the healthy normal mouse strains. On the other hand, CDS+ B cell population in the peripheral blood, which were reported to be increased with the development of RA for human, was rather significantly decreased for the CIA-induced DBA/lJCrj mice as evidenced by FACS analysis. It could be due to the differences in the pathogenic mechanism between CIA and RA. Taken together, our results. suggest that the levels of both these cytokines and CDS+ B cells may be utilized as important diagnostic markers for arthritides.

Effects of Chung-Pae Inhalation Therapy on a Mouse Model of Chronic Obstructive Pulmonary Disease

Hwang, Joon-Ho,Lee, Beom-Joon,Jung, Hee Jae,Kim, Kwan-Il,Choi, Jun-Yong,Joo, Myungsoo,Jung, Sung-Ki Hindawi Publishing Corporation 2015 Evidence-based Complementary and Alternative Medic Vol.2015 No.-

<P>Chung-pae (CP) inhalation therapy is a method frequently used in Korea to treat lung disease, especially chronic obstructive pulmonary disease (COPD). This study investigated the effects of CP inhalation on a COPD animal model. C57BL/6 mice received porcine pancreatic elastase (PPE) and lipopolysaccharide (LPS) alternately three times for 3 weeks to induce COPD. Then, CP (5 or 20 mg/kg) was administered every 2 h after the final LPS administration. The effect of CP was evaluated by bronchoalveolar lavage (BAL) fluid analysis, histological analysis of lung tissue, and reverse transcription polymerase chain reaction analysis of mRNA of interleukin- (IL-) 1<I>β</I>, tumor necrosis factor- (TNF-) <I>α</I>, IL-6, and tumor growth factor- (TGF-) <I>β</I>. Intratracheal CP administration reduced the number of leukocytes and neutrophils in BAL fluid, inhibited the histological appearance of lung damage, and decreased the mRNA levels of the proinflammatory cytokines IL-1<I>β</I>, TNF-<I>α</I>, IL-6, and TGF-<I>β</I>. Intratracheal CP administration effectively decreased the chronic inflammation and pathological changes in a PPE- and LPS-induced COPD mouse model. Therefore, we suggest that CP is a promising strategy for COPD.</P>

Ginsenoside Rg1 enhances CD4^(+) T-cell activities and modulates Th1/Th2 differentiation

Lee, Eui-joon,Ko, Eunjung,Lee, Jinwoo,Rho, Samwoong,Ko, Seonggyu,Shin, Min-Kyu,Min, Byung-il,Hong, Moo-Chang,Kim, Si-young,Bae, Hyunsu WHO COLLABORATING CENTRE FOR TRADITIONAL MEDICINE 2003 東西醫學硏究所 論文集 Vol.2003 No.-

Panax ginseng is commonly used as a tonic medicine in Asian countries such as Korea, China, and Japan. It has been reported that ginsenoside Rg1 in P. ginseng increases the proportion of T helper(Th) cells among the total number of T cells and promotes IL-2 gene expression in murine splenocytes. This implies that ginsenoside Rg1 increases the immune activity of CD4 T cells, however, the exact mechanism remains unknown. The present study elucidated the direct effect of Rg1 on helper T-cell activities and on Th1/Th2 lineage development. The results demonstrated that ginsenoside Rg1 had no mitogenic effects on unstimulated CD4^(+) T cells, but augmented CD4^(-) T-cell proliferation upon activation with anti-CD3/anti-CD28 autibodies in a dose-dependent manner. Rg1 also enhanced the expression of cell surface protein CD69 on CD4^(-) T cells. In Th0 condition, ginsenoside Rg1 increases the expression of IL-2 mRNA, and enhances the expression of IL-4 mRNA on CD4^(+) T cells, suggesting that Rg1 prefers to induce Th2 lineage development. In addition, ginsenoside Rg1 increases IL-4 secretion in CD4^(+) T cells under Th2 skewed condition, while decreasing IFN-ysecretion of cells in Th1 polarizing condition. Thus, Rg1 enhances Th2 lineage development from the naive CD4^(+) T cell both by increasing Th2 specific cytokine secretion and by repressing Th1 specific cytokine production. Therefore, these results suggest that ginsenoside Rg1 is a desirable agent for enhancing CD4^(-) T-cell activity, as well as the correction of Th1-dominant pathological disorders.

TLR4, 5, and 9 Agonists Inhibit Murine Airway Invariant Natural Killer T Cells in an IL-12-Dependent Manner

Jae-Uoong Shim,Joon Haeng Rhee,Young-Il Koh 대한천식알레르기학회 2012 Allergy, Asthma & Immunology Research Vol.4 No.5

Purpose: Invariant natural killer T (iNKT) cells may play an important role in the pathogenesis of asthma in mice and humans. Thus, an agent that modulates the function of iNKT cells may have therapeutic potential to control asthma. We hypothesized that lipopolysaccharide (LPS)-, flagellin-, or CpG-induced changes in the cytokine milieu may modify and even inhibit the function of airway iNKT cells in asthma. Methods: Because increased α-galactosylceramide (GalCer)-induced airway hyperreactivity (AHR) reflects the presence of airway iNKT cells, α-GalCer-induced AHR, as well as inflammatory cells and cytokines in bronchoalveolar lavage (BAL) fluid, were determined 24 hours after in vivo treatment with LPS, flagellin, or CpG in naïve BALB/c mice. Intracellular IL-4 and IFN-γ were measured in spleen iNKT cells after in vitro treatment with LPS, flagellin, or CpG. A role for IL-12 following the treatments was determined. Results: Intranasal administration of LPS, flagellin, or CpG reduced development of α-GalCer-induced AHR, eosinophilic airway inflammation, and Th1 and Th2 cytokine responses in BAL fluid, while producing IL-12 in BAL fluid. Intraperitoneal administration of IL-12 mAb blocked the suppressive effect of LPS, flagellin, or CpG. In vitro treatment with LPS, flagellin, or CpG reduced production of IL-4 and IFN-γ from α-GalCer-stimulated spleen iNKT cells; these effects were ameliorated by addition of anti-IL-12 mAb. Conclusions: TLR4, 5,and 9 agonists may suppress the function of airway and spleen iNKT cells via IL-12-dependent mechanisms. Anergy of iNKT cells by IL-12 might play a role in suppression by these TLR agonists.

금은화(金銀花) 및 금은화전초(金銀花全草)가 Raw 264.7 cell에서 LPS로 유도된 NO의 생성, iNOS, COX-2 및 cytokine에 미치는 영향

이동언,이재령,김영우,권영규,변성희,신상우,서성일,권택규,변준석,김상찬,Lee, Dong-Eun,Lee, Jae-Ryung,Kim, Young-Woo,Kwon, Young-Kyu,Byun, Sung-Hui,Shin, Sang-Woo,Suh, Seong-Il,Kwon, Taeg-Kyu,Byun, Joon-Seok,Kim, Sang-Chan 대한동의생리학회 2005 동의생리병리학회지 Vol.19 No.2

Lonicerae Flos has antibacterial effects against Staphylococcus aureus, streptococci, pneumococci, Bacillus dysenterii, Salmonella typhi, and paratyphoid. It is an antiviral agent. The herb has a cytoprotective effect against $CCl_{4}-induced$ hepatic injury. It has antilipemic action, interfering with lipid absorption from the gut. Nowadays this herb is used mainly in the treatment of upper respiratory infections, such as tonsillitis and acute laryngitis. It is also used in the treatment of skin suppurations, such as carbuncles, and to treat viral conjunctivitis, influenza, pneumonia, and mastitis. Lonicerae Flos is dried flower buds of Lonicera japonica, L. hypoglauca, L. confusa, or L. dasystyla. But, for the most part, we use whole plant of Lonicera japonica, as a flower bud of it. And, little is known of the original copy of effects of whole plant, except for the 'Bon-Cho-Gang-Mok', which is written the effects of flower of Lonicera japonica are equal to effects of leaves and branch of it. The present study was conducted to evaluate the effect of flower and whole plant of Lonicera japonica on the regulatory mechanism of cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) for the immunological activities in Raw 264.7 cells. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, flower and whole plant of Lonicera japonica water extracts inhibited nitric oxide production in a dose-dependent manner and abrogated iNOS and COX-2. Flower and whole plant of Lonicera japonica water extract did not affect on cell viability. To investigate the mechanism by which flower and whole plant of Lonicera japonica water extract inhibits iNOS and COX-2 gene expression, we examined the on phosphorylation of inhibitor ${\kappa}B{\alpha}$ and assessed production of $TNF-{\alpha}$, $interleukin-1{\beta}$ $(IL-1{\beta})$ and interleukin-6 (IL-6). Results provided evidence that flower and whole plant of Lonicera japonica inhibited the production of $IL-1{\beta}$, IL-6 and activated the phosphorylation of inhibitor ${\kappa}B{\alpha}$ in Raw 264.7 cells activated with LPS. These findings suggest that flower and whole plant of Lonicera japonica can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections, respectively.

Henoch-$Sch\ddot{o}nlein$ Purpura에서 Interleukin $1{\beta}$ 유전자 다형성과 신장 침범과의 연관성

나형준,고일용,윤준호,예병일,김황민,Na, Hyoung-Joon,Go, Il-Yong,Yoon, Joon-Ho,Yeh, Byung-Il,Kim, Hwang-Min 대한소아신장학회 2006 Childhood kidney diseases Vol.10 No.2

Purpose : High interleukin-1 beta(IL-$1{\beta}$) expression in the skin biopsy specimens of patients with Henoch-$Sch\ddot{o}nlein$ Purpura(HSP) has been observed. We examined IL-$1{\beta}$ gene polymorphism in patients with HSP. The purpose of this study is to examine the relationship between IL-$1{\beta}$ gene polymorphism and renal involvement in HSP. Methods : Patients from mideast Korea with HSP were studied. All patients had at least 6 months of follow up. Patients and ethnically matched controls were genotyped for IL-$1{\beta}$ gene polymorphism by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP). Results : Thirty-four patients(all younger than 15 years old) who had been diagnosed with HSP and 27 controls were examined. No allele or genotype differences between the HSP and control groups were observed. No significant association between the carriage of IL-$1{\beta}$(-511) T allele and renal involvement(P=0.525, OR:1.417, CI:0.545-3.686) was found. Conclusion : In unselected patients with HSP, carriage of IL-$1{\beta}$(-511) T allele does not appear to influence renal involvement.

A Novel Function of Interleukin-10 Promoting Self-Renewal of Hematopoietic Stem Cells

Kang, Young-Ju,Yang, Seung-Jip,Park, Gyeongsin,Cho, Bin,Min, Chang-Ki,Kim, Tae-Yoon,Lee, Joon-Sung,Oh, Il-Hoan Wiley (John WileySons) 2007 Stem Cells Vol.25 No.7

<P>Self-renewal of hematopoietic stem cells (HSCs) is key to their reconstituting ability, but the factors regulating the process remain poorly understood. Here, we show that Interleukin-10 (IL-10), a pleiotropic immune modulating cytokine, can also play a role in regulating HSC self-renewal. First, a quantitative decrease of primitive hematopoietic cell populations, but not more matured cells, was observed in the bone marrows of IL-10 disrupted mice as determined by long-term in vitro cultures or in vivo competitive repopulation assays. In contrast, normal HSCs from 5-fluorouracil treated marrows cultured on the IL-10 secreting stroma displayed an enhanced repopulating activity compared with cells grown on control stroma, with ninefold higher numbers of donor-derived HSCs in the reconstituted recipient marrows. Moreover, limiting dilution transplantation assay demonstrated that exogenous addition of IL-10 in the stroma-free cultures of purified Lin- Sca-1+ c-kit+ cells caused three- to fourfold higher frequencies of HSCs in the 5-day short-term culture without indirect inhibitory effect of IL-10 on tumor necrosis factor-alpha or interferon-gamma secretion. Interestingly, primitive hematopoietic cells, including Lin- Sca-1+ c-kit+ or side population cells, expressed the surface receptor for IL-10, and microenvironmental production of IL-10 was sharply increased in the osteoblasts lining the trabecular regions of the radiation-stressed marrow but not in the steady-state marrows. These results show that IL-10 may be a ligand that can stimulate self-renewal of HSCs to promote their regeneration in addition to being a ligand for immune regulation. Disclosure of potential conflicts of interest is found at the end of this article.</P>