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      • SCIESCOPUS

        Impact of interleukin-21 in the pathogenesis of primary Sjogren's syndrome: increased serum levels of interleukin-21 and its expression in the labial salivary glands

        Kang,,Kwi,Young,Kim,,Hyun-Ok,Kwok,,Seung-Ki,Ju,,Ji,Hyeon,Park,,Kyung-Su,Sun,,Dong-Il,Jhun,,Joo,Yeon,Oh,,Hye,Jwa,Park,,Sung-Hwan,Kim,,Ho-Youn BioMed Central 2011 ARTHRITIS RESEARCH AND THERAPY Vol.13 No.5

        <P><B>Introduction</B></P><P>Interleukin (IL)-21 is a cytokine that controls the functional activity of effector T helper cells and the differentiation of Th17 cells, and promotes B-cell differentiation. To test whether IL-21 participates in the pathogenesis of primary Sjögren's syndrome (SS), serum IL-21 level was measured and IL-21 expression in the labial salivary glands (LSG) was examined.</P><P><B>Methods</B></P><P>Serum IL-21 levels in 40 primary SS, 40 rheumatoid arthritis (RA), and 38 systemic lupus erythematosus (SLE) patients and 20 healthy controls were measured. Serum IL-21 levels of SS patients were assessed for correlations with laboratory data, including anti-nuclear antibody, anti-Ro/La antibodies, globulin, immunoglobulin (Ig) class, and IgG subclass. LSGs from 16 primary SS and 4 controls with sicca symptoms were evaluated for IL-21 and IL-21 receptor (IL-21R) expression by immunohistochemistry. Confocal microscopy was performed to further characterize the IL-21 positive cells.</P><P><B>Results</B></P><P>Primary SS patients had significantly higher serum IL-21 levels than controls, and these increments correlated positively with levels of IgG, IgG1. Serum IgG1 levels correlated with anti-Ro antibody titers. Immunohistochemical analyses showed that lymphocytic foci and the periductal area of the LSGs from SS patients expressed high levels of IL-21 and lower levels of IL-21R, whereas the control LSGs showed minimal expression of both antigens. The more the lymphocyte infiltrated, IL-21expression in LSGs showed a tendency to increase. Confocal microscopic analyses revealed that IL-21 expressing infiltrating lymphocytes in the LSGs of SS patients also expressed CXCR5.</P><P><B>Conclusions</B></P><P>Primary SS is associated with high serum IL-21 levels that correlate positively with serum IgG, especially IgG1, levels. The expression of IL-21 is increased as more lymphocytes infiltrated in LSGs. These observations suggest that IL-21 may play an important role in primary SS pathogenesis.</P>

      • KCI등재

        원저 : IL-15에 의한 류마티스관절염 환자 활막 섬유모세포에서의 SDF-1 유도

        박영은 ( Young Eun Park ), 김성일 ( Sung Il Kim ), 박성후 ( Seong Hu Park ), 백승훈 ( Seung Hoon Baek ), 오혜좌 ( Hye Jwa Oh ), 허양미 ( Yang Mi Heo ), 조미라 ( Mi La Cho ) 대한류마티스학회 2010 대한류마티스학회지 Vol.17 No.3

        Objective: Interleukin-15 (IL-15) recruits and activates synovial T cells, and IL-15 plays an important role in amplifying and perpetuating inflammation in the pathogenesis of rheumatoid arthritis (RA). Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for memory T cells in the inflamed RA synovium. This study investigated the effect of IL-15 on SDF-1 production in RA fibroblast-like synoviocytes (FLS). Methods: The expressions of IL-15 and SDF-1 were determined from the synovium of patients with RA and osteoarthritis (OA) by performing immunohistochemistry. The expressions of SDF-1 was measured from the RA FLS that were cultured with IL-15 and IL-17 by real-time RT-PCR and ELISA. The SDF-1 expression was also measured, via ELISA, from the RA FLS stimulated by IL-15 together with the inhibitors of such intracellular signal molecules as phosphatidylinositol 3-kinase (PI 3-kinase, LY294002), STAT3 (AG490), MAP Kinase (PD98059), NF-κB (parthenolide) and activator protein 1 (AP-1, curcumin). Results: IL-15 and SDF-1 were mainly expressed in the RA synovium compared to that of the OA synovium. IL-15 increased the SDF-1 expressions and it, and had an additive effect with IL-17 on the SDF-1 expressions in the cultured RA FLS. The IL-15 induced increase of the SDF-1 expression in the cultured RA FLS was blocked by the inhibitors of PI 3-kinase, NF-κB and AP-1. Conclusion: The SDF-1 expression was increased in the RA synovium and it was up-regulated by IL-15 in the RA FLS through the PI 3-kinase, NF-κB, and AP-1 pathways. These results imply that the IL-15 induced increase of the SDF-1 expressions may be involved in the immunopathogenesis of RA.

      • Identification of cytokines inhibiting eosinophil activation and the inhibitory mechanism

        Park,,Choon-Sik,Choi,,Eun,Nam,Lee,,Young,Mok,Park,,Sung,Woo,Jang,,An,Soo,Lee,,June,Hyuk,Choi,,Yun,Sung,Chung,,Il,Yup 대한천식 및 알레르기학회 2003 천식 및 알레르기 Vol.23 No.4

        IL-5는 여러 경로를 통하여 호산구의 기능에 결정적인 역할을 하고 혈액이나 조직에서 호산구의 수적인 증가를 고려할 때 호산구 증다증을 동반하는 여러 질환과 깊게 연관되어 있다. 본 실험에서 IL-5로 자극된 호산구와 자극되지 않은 호산구의 활성을 pro-inflammatory cytokines(IL-1β , IL-6, TNF-α )과 Th1(IFN- γ), Th2(IL-4, IL-13) 그리고 Tr cytokines(IL-10)이 억제할 수 있는지를 eosinophil shape change를 통해서 알아보았다. 시간과 투여량에 따라 IL-6와 TNF- 는 자극되지 않은 호산구의 크기를 증가시키는 반면, IFN- γ와 IL-4 그리고 IL-13은 호산구의 크기를 유의하게 감소시켰다. 또한 IL-13을 제외한 IFN- γ와 IL-4는 IL-5로 자극된 호산구의 shapec hange를 억제했다. 최대 억제를 위해서 IFN- γ와 IL-4로 30~60분 정도 전처리 하였다. cyclohexamide에 의한 억제 효과의 제거는 cytokine에 의한 신호전달과 IFN- γ의 효과에 있어서 새로운 단백질이 필요함을 제시하였다. IFN- γ의 전처치는 IL-5에 의하여 유도된 ERK1/2의 인산화를 유의하게 억제하였다. 결론적으로 IFN- γ는 새로운 단백질의 생성으로 MAP kinase 활성을 억제하여 IL-5로 자극된 호산구의 기능을 조절할 수 있다. (J Asthma Allergy Clin Immunol 23: 759-72, 2003)

      • A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130

        Hong,,Soon-Sun,Choi,,Jung,Ho,Lee,,Sung,Yoon,Park,,Yeon-Hwa,Park,,Kyung-Yeon,Lee,,Joo,Young,Kim,,Juyoung,Gajulapati,,Veeraswamy,Goo,,Ja-Il,Singh,,Sarbjit,Lee,,Kyeong,Kim,,Young-Kook,Im,,So,Hee,Ahn,,Sun The American Association of Immunologists, Inc. 2015 JOURNAL OF IMMUNOLOGY Vol.195 No.1

        <P>IL-6 is a major causative factor of inflammatory disease. Although IL-6 and its signaling pathways are promising targets, orally available small-molecule drugs specific for IL-6 have not been developed. To discover IL-6 antagonists, we screened our in-house chemical library and identified-LMT-28, a novel synthetic compound, as a candidate IL-6 blocker. The activity, mechanism of action, and direct molecular target of LMT-28 were investigated. A reporter gene assay showed that LMT-28 suppressed activation of STAT3 induced by IL-6, but not activation induced by leukemia inhibitory factor. In addition, LMT-28 downregulated IL-6-stimulated phosphorylation of STAT3, gp130, and JAK2 protein and substantially inhibited IL-6-dependent TF-1 cell proliferation. LMT-28 antagonized IL-6-induced TNF-alpha production in vivo. In pathologic models, oral administration of LMT-28 alleviated collagen-induced arthritis and acute pancreatitis in mice. Based on the observation of upstream IL-6 signal inhibition by LMT-28, we hypothesized IL-6, IL-6R alpha, or gp130 to be putative molecular targets. We subsequently demonstrated direct interaction of LMT-28 with gp130 and specific reduction of IL-6/IL-6R alpha complex binding to gp130 in the presence of LMT-28, which was measured by surface plasmon resonance analysis. Taken together, our data suggest that LMT-28 is a novel synthetic IL-6 inhibitor that functions through direct binding to gp130.</P>

      • SCIESCOPUSKCI등재후보

        Articles : Up - Regulation of Interleukin - 4 Receptor Expression by Interleukin - 4 and CD40 Ligation via Tyrosine Kinase - Dependent Pathway

        ( Hyun Il Kim Eui Young So Suk Ran Yoon Mi Young Han Choong Eun Lee ) 한국생화학분자생물학회 (구 한국생화학회) 1998 BMB Reports Vol.31 No.1

        Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4(IL-4) and CD40 ligation in B cell activation we have examined the effect of CD40 cross-linking on the IL-40 receptor expression in human B cells using anti-CD40 antibody. We observed that IL-4 and anti-CD40 both induce IL-40 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in asignificant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

      • KCI등재후보

        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.

      • 화상환자에서 면역억제 기전

        정태호,황일우,장수일,김문규,서정민,정치영,김정철 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.4

        목적 : 본 연구는 화상환자에서 면역이상의 기전을 조사코져 T-세포의 활성을 나타내는 가용성 interleukin-2 수용체(IL-2R), 대식세포의 활성을 나타내는 neopterin, tumor necrosis factor(TNF) 및 interleukin-6 (IL-6), 그리고 호중구의 활성을 반영하는 elastase-α1-antitrypsin을 측정하였다. 또한 lipopolysaccharide(LPS)가 이들 면역세포의 활성화에 미치는 영향을 조사하였다. 대상 및 방법 : 30예의 화상환자를 대상으로 화상후 1일, 7일, 14일, 21일, 28일에 각각 혈액을 채취하여 혈청중 가용성 IL-2R, TNF, IL-6, 그리고 elastase-α1-antitrypsin은 각각 효소면역법으로, 혈청중 neopterin은 radioimmunoassay법으로 측정하였다. LPS가 말초 단핵세포에 미치는 영향은 역전사 중합효소 연쇄반응을 통하여 각종 cytokines의 mRNA 발현을 측정하였다. 결과 : 화상환자에서 혈청중 가용성 IL-2R은 화상후 1일째부터 대조군에 비하여 유의성 있게 증가되어 7일과 14일째에 최고치를 나타냈으며 그 이후에는 다소 감소하였으나 대조군보다는 유의한 증가를 나타냈다. 화상환자를 중화상, 중등도화상, 경도화상으로 분류하여 혈청중 가용성 IL-2R 치를 비교해본 결과 중증 화상일수록 더욱 높은 치를 나타냈다. 화상환자에서 혈청중 neopterin 역시 화상후 1일째부터 증가되어 전 관찰기간 동안 대조군에 비해 유의한 높은 치를 나타냈다. 경도화상과 중등도 화상에서는 서로 유의한 차이를 보이지 않았으나 중환자에서는 경도 혹은 중등도 화상환자에 비해 유의한 증가를 보였다. 화상환자에서 혈청중 TNF 농도는 화상후 1일부터 증가되어 관찰전기간에 걸쳐 유의한 증가를 나타냈으며 중등도 화상환자에서 가장 높은 치를 보였다. 혈청중 IL-6치 역시 화상 전기간에 걸쳐 대조군보다 유의한 증가를 나타냈으며 중화상 환자에서 가장 높은 치를 나타냈다. 화상은 또한 혈청중 elastase-α1-antitrypsin 농도를 현저히 증가시켰다. 즉 화상후 1일에 elastase-α1-antitrypsin 농도는 정상인보다 5배 높았으며 그 이후 약 4주간 계속 높은 농도를 유지하다가 환자가 회복되면서 감소하는 경향을 나타내었다. 중등도화상 및 중화상환자의 혈청중 elastase-α1-antitrypsin 농도는 경도 화상환자에서 비해 유의한 증가를 보였다. 한편 화상환자에서 면역이상을 초래하는 주된 요인으로 여겨지는 lipopolysaccharide는 면역세포를 총체적으로 활성화시켜 IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF, IFN-γ, TGF-β, GM-CSF, IL-2R의 유전자발현을 현저히 증가시켰다. 결론 : 화상환자에서 T-세포, 대식세포, 호중구의 활성화를 반영하는 가용성 IL-2R, neopterin, ,TNF, IL-6, elastase-α1-antitrypsin치가 혈중에 증가되어 있으며 화상의 정도가 심할수록 더 높았다. Cell-mediated immunity frequently becomes severely impaired after thermal injury. However, the cause of postburn immune dysfunction is unclear and controversy exists over both pathophysiology and clinical relevance of these abnormalities. This study was undertaken to investigate the immune responses in vivo of patients with burn. Levels of soluble IL-2R, a sensitive marker of T-cell activation, levels of serum TNF, IL-6, and neopterin, an index of macrophage activation, and levels of serum elastase-α1-antitrypsin, an index of neutrophil activation, were measured in serial serum samples taken from 30 burned patients. In patients with burn, soluble IL-2R levels were increased over a 4-week interval with peak concentrations reached during the 2nd week after burn. Patients with severe burn showed a higher soluble IL-2R levels than those with mild or moderate burn. In addition soluble IL-2R significantly correlated with burn size. The levels of serum neopterin were already increased at the first day following burn, and remained at a high level throughout the total period studied (28 days). Patients with severe burn showed significantly higher concentration of serum neopterin than mild or moderate burn. There was positive relationship between the burn sizes and the levels of neopterin. A significant positive correlation was also found between serum soluble IL-2R levels and neopterin levels in burn patients. Levels of serum TNF and IL-6 were also significantly increased over a 4-week interval in burn patients. The levels of serum elastase-α1-antitrypsin were also already increased at the first day following burn, and remained at a high level over a 4-week. Patients with moderate or severe burn showed significantly higher concentration of serum elastase-α1-antitrypsin than those with mild burn. There was no significant relationship between the burn extent and the level of elastase-α1-antitrypsin. LPS increased the transcription of all the cytokines we examined in peripheral mononuclear cells, i.e., IL-1α, IL-1β, IL-2, IL-4, IL-5_IL-6, IL-8, IL-10, TNF, TGF-β, GM-CSF, and IL-2R. We conclude that soluble IL-2R, neopterin, TNF, IL-6, and elastase-α1-antitrypsin might be useful parameters for monitoring of the clinical course in burn patients. Moreover, they indicate that T-cell, macrophage, and neutrophil activation might play the central role in the pathogenesis of the immuno-logic and metabolic disturbance that follows thermal injury.

      • 金正日體制管理經綸과 그 延命術 : North Korean Power Politics since 1974- An Analysis Kim, Jong Il's Statecraft on System Management and his Tactics of Survival 1974년이래의 북한판 "勢道政治"

        신일철 고려대학교 북한학연구소 2000 北韓學硏究 Vol.1 No.-

        When the lord reigned but did not rule, we called the period as being under the power politics. The lord was simply a figure-head of the feudal dynasty without any power at all. Since 1974, a similar power politics has been in existence in North Korea; Kim Il Sung was raised as the founder of the pseudo-religious sect, while his son, Jong Il, governed in the name or his father's charisma. It is this type of modem power politics that Kim Jong Il managed in the apex of the power structure, where his power and authority was supported and maintained by the personality worship towards his father by his people. Kim Jong Il's ruling tactics has mainly consisted of the cult of personality, and the mobilization structure led by the monolithic and dogmatic doctrine of the Suryong (the leader). This cult of personality also managed to take the heart and soul fo the people into a dictatorial system through the routine process of instigating propaganda and ideological lessons. Kim Jong Il's management tactics in the 1970s were mostly devoted to mobilizing or exploiting human labor forces via political and ideological means such as Speed Battle (Campaign). Directed by his The Great Three Revolution Tennis (Samdae Hyongmyong), it blocked the road towards medium-ranged development. Therefore, it was natural that the inter-Korea economic contest turned out up side down between Seoul and Pyongyang, and the economic capability of the North dropped to just one twenty-fifth of the South's. Kim Jong Il's political ideology is the Suryong doctrine. The Suryong is not only a respectful title of a supreme leader; rather, he is very much like an absolute, despotic monarch over the constitution, or a founder of a pseudo-religious sect putting a great emphasis on the deity of the leader Ever since the purge of the Kapsan faction, Kim Jong Il took on the interpretation of the Marxism-Leninism and the rights of initiating and developing the dogmatic Juche ideology, the DPRK's ruling ideology. In the early 1990s, Kim Jong Il's leadership faced a serious challenge due to the sudden collapse of socialistm in Eastern Europe and the USSR along with the reform and opening in China and Vietnam. However, Kim Jong Il reacted firmly against such reform and opening movements under tile slogan of "Our Way of Socialism." In addition, Kim Jong Il developed the concept of the Immortal Socio-Political Organic Body, which means that the masses are to be integrated into the socio-political body politic that is destined to live forever, While physical life, which is mortal, is given by the parents, political life, which is immortal, is given by this socio-political body. Therefore, the masses are required to unconditionally obey the brain of the organic body, which is the Suryong. Furthermore, Kim Jong Il demanded the people not just to obey, but to be determined to flight until death. This is all in attempt to protect the Suryong. This kind of deplorable death or glory spirit is one of the basic elements of the DPRK policies of survival, and the brinkmanship reflected in the DPRK-US direct talks. Regardless, Kim Jong Il has four major shortcomings in his management tactics; Firstly, the overemphasis on the charisma of Kim Il sung has become dysfunctional, and thus, it is very difficult to justify the doctrine of personality worship towards Kim Jlong Il. Secondly, from the viewpoint of the dual social structure based on Marxism and Leninism, the lower structure in the DPRK has collapsed, and the upper structure, including the Party, the Government, and even the administrative organs, has been collapsing step by step except the Military. Thirdly, the adoption of the People's Economic Planning Law signifies that Pyongyang has chosen a central planning and ordering instead of market and civil society, and thus, made it difficult to predict which way the North Korean regime would follow. Fourthly and lastly, Kim Jong Il's system is now facing a deadlock by sticking to such an isolated and closed garrison state, which is totally outdated in the era of postcold war and information revolution.

      • Interleukin 17 (IL-17) Increases the Expression of Toll-like Receptor-2, 4, and 9 by Increasing IL-1β and IL-6 Production in Autoimmune Arthritis

        LEE,,JUN-HEE,CHO,,MI-LA,KIM,,JU-IN,MOON,,YOUNG-MEE,OH,,HYE-JWA,KIM,,GEUN-TAE,RYU,,SUN,BAEK,,SEUNG-HOON,LEE,,SUN-HEE,KIM,,HO-YOUN,KIM,,SUNG-IL The Journal of Rheumatology 2009 The Journal of rheumatology Vol.36 No.4

        <B>Objective.</B><P>To examine the effect of interleukin 17 (IL-17) on the expression of Toll-like receptor (TLR)-2, 4, and 9 in collagen-induced arthritis (CIA) in mice.</P><B>Methods.</B><P>On Days 28 and 32 after induction of CIA in mice, phosphate-buffered saline (PBS group) or IL-17 (IL-17 group) was injected into both knee joints. On Day 35, mice were sacrificed. The severity of knee joint arthritis, synovial inflammation, and bone destruction was measured by a scoring system using macrography and histological analysis. Synovial expression of TLR-2, 4, 9, IL-17, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-6 was determined by real-time PCR and immunohistochemistry. Synoviocytes of CIA mice were cultured with IL-17 and with neutralizing antibodies to cytokine, and the expression of TLR-2, 4, 9, IL-1ß, TNF-α, and IL-6 was determined by real-time RT-PCR.</P><B>Results.</B><P>In CIA mice, knee arthritis scores, synovial inflammation, bone destruction scores, and expression of synovial TLR-2, 4, and 9, IL-17, IL-1ß, TNF-α and IL-6 were higher in the IL-17 and PBS groups than in normal DBA1 mice. These variables were also significantly higher in the IL-17 group than in the PBS group. In CIA synoviocytes, IL-17 increased the expression of TLR-2, 4, and 9, and this effect was significantly alleviated by neutralizing antibodies to IL-17, IL-1ß, and IL-6.</P><B>Conclusion.</B><P>IL-17 aggravates joint inflammation and destruction, and increases the synovial expression of TLR-2, 4, and 9 by increasing IL-1ß and IL-6. These results imply that the IL-17-induced increase in expression of TLR-2, 4, and 9, and IL-1ß and IL-6 production are involved in the IL-17-induced aggravation of arthritis.</P>

      • Up-Regulation of Interleukin-4 Receptor Expression by Interleukin-4 and CD40 Ligation via Tyrosine Kinase-Dependent Pathway

        Kim,,Hyun-Il,So,,Eui-Young,Yoon,,Suk-Ran,Han,,Mi-Young,Lee,,Choong-Eun Korean Society for Biochemistry and Molecular Biol 1998 Journal of biochemistry and molecular biology Vol.31 No.1

        Recently a B cell surface molecule, CD40, has emerged as a receptor mediating a co-stimulatory signal for B cell proliferation and differentiation. To investigate the mechanism of synergy between interleukin-4 (IL-4) and CD40 ligation in B cell activation, we have examined the effect of CE40 cross-linking on the IL-4 receptor expression in human B cells using anti-CE40 antibody. We observed that IL-4 and anti-CD40 both induce IL-4 receptor gene expression with a rapid kinetics resulting in a noticeable accumulation of IL-4 receptor mRNA within 4 h. While IL-4 caused a dose-dependent induction of surface IL-4 receptor expression, the inclusion of anti-CD40 in the IL-4-treated culture, further up-regulated the IL-4-induced IL-4 receptor expression as analyzed by flow cytometry. Pretreatment of B cells with inhibitors of protein tyrosine kinase (PTK) resulted in a significant inhibition of both the IL-4- and anti-CD40-induced IL-4 receptor mRNA levels, while protein kinase C (PKC) inhibitors had no effects. These results suggest that IL-4 and CD40 ligation generate B cell signals, which via PTK-dependent pathways, lead to the synergistic induction of IL-4 receptor gene expression. The rapid induction of IL-4 receptor gene expression through the tyrosine kinase-mediated signal transduction by B cell activating stimuli, would provide cells capacity for an efficient response to IL-4 in the early phase of IL-4 action, and may in part constitute the molecular basis of the reported anti-CD40 co-stimulatory effect on the IL-4-induced response.

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