Ishikawa, Osamu

Motegi, Sei-ichiro

Perera, Buddhini

Uchiyama, Akihiko

Uehara, Akihito

Yamada, Kazuya

English

Institutional Repositories DataBase (IRDB)

Mechanisms of ATP-induced IL-6 Production in Systemic Sclerosis Fibroblasts

Gunma University Academic Information Repository

手指潰瘍と末節骨短縮を有する強皮症患者の血清アペリン量は有意に低下していた.以上の結果から,アペリンが線維芽細胞の線維化を抑制し,その発現低下が強皮症の病態に関与している可能性が示唆された.12．Mechanisms of ATP-induced IL-6Production in Systemic Sclerosis Fibroblasts Buddhini Perera,Akihiko Uchiyama,Kazuya Yamada,Akihito Uehara,Osamu Ishikawa and Sei-ichiro Motegi（Department of Dermatology,Gunma Univer-sity Graduate School of Medicine）【Background&Objective】 Systemic sclerosis(SSc)is a connective tissue disorder characterized by the development of fibrosis in the skin and internal organs as wel as microvascular dysfunction. It has been considered that vasculopathy induces hypoxia and oxidative stress in the dermis in SSc.ATP(adenosine triphosphate)is released from fibroblasts and endothelial cels by tissue injury/hypoxia,however,the role of ATP in the pathogenesis of skin fibrosis in SSc is unknown.IL-6 is a potent stimulator of colagen synthesis in fibroblasts.Objective was to eluci-date the mechanisms of ATP-induced IL-6 production in SSc fibroblasts.【Results】 IL-6 mRNA levels in the normal and SSc fibroblasts increased after ATP stimulation.In addition,the IL-6 mRNA levels in the SSc fibroblasts treated with ATP were significantly higher than those in the normal fibroblasts.Non-selective P2 receptor(P2R)antagonist,suramin significantly inhibited the ATP-induced IL-6 expression in the SSc fibroblasts.The phosphorylation of p38 in SSc fibroblasts was significantly enhanced by ATP,and the ATP-induced p38 phosphorylation was also inhib-ited by suramin. Furthermore,the ATP-induced IL-6 production in the SSc fibroblasts was significantly inhibited by the p38 inhibitor,SB203580.Combined treatment with ATP and norepinephrine resulted in an additive increase in the production of IL-6 in the SSc fibroblasts.【Conclusion】 ATP binds to and activates the downstream signaling of P2R,thus leading to the phosphorylation of p38.This ATP-induced activation of p38 signaling may consequently enhance IL-6 production in SSc fibroblasts.P2R blocker,suramin,and the p38 inhibitor,SB203580,both inhibited the ATP-induced IL-6 production in SSc fibroblasts in vitro,suggesting that P2R blocker and/or p38 inhibitor therapy can be an alternative treatment for skin sclerosis in patients with SSc.13．加圧光センサを用いた強皮症の末梢循環障害評価装置山越 芳樹?，茂木精一郎?，石川 治?（１ 群馬大学理工学府 電子情報部門）（２ 群馬大院・医・皮膚科学）全身性強皮症は,皮膚および内蔵臓器の線維化,血管障害,免疫異常を特徴とする全身性疾患である.末梢血管機能障害によって,レイノー現象,手指潰瘍,壊疽が生じるため,病態の評価や治療効果判定に適した新たな末梢血管機能評価装置の開発が切望されている.今回,我々は,末梢血管機能を数値化して評価できる新たな装置として,?加圧光センサ法」を用いた装置を開発した.これは,反射型の多色の光センサを用い,一定圧で加圧した時に生じる末梢循環系からの血液流失,および加圧力を弱めた後の血液再灌流時の受光強度の変化を測定する方法である.本装置の有効性を検証する臨床研究を医師主導臨床試験として群馬大学IRBの承認の下で群馬大学医学部附属病院皮膚科において健常者 :30名,強皮症患者 :30名に対して実施した.測定では一次圧を309 mmHgに固定し,2次圧を109,88,64,53,40,28 mmHgと変化させて血液の末梢血管系への再充満量を観測した.その結果,健常者に比べて,強皮症患者では二次圧印加時の拍動信号の消滅と血液再充満量の著しい減少が観測された.また,二次圧を40 mmHgとした時の血液再充満量では,皮膚硬化の強い強皮症患者でより低下する傾向がみられた.これらの結果より,強皮症患者では,末梢循環系の血管抵抗の増大に伴う末梢循環障害が示唆された.また,本手法は,強皮症における末梢循環障害の評価装置として有用と考えられた.本手法は簡便で,3被験者に負担を強いることがなく短時間で検査が終了する新たな検査法であるために,強皮症の診断だけでなく臨床研究の進展により動脈硬化や高血圧等の生活習慣病に繫がる末梢循環評価や血管内皮細胞評価のための手法になることが期待される.14．Non-invasive Quantitative Evaluation of Cerebral Blood Flow (CBF)Using Technetium Labeled Ethyl Cysteinate Dimer(???Tc-ECD):Performance of Aorta’s Region of Interest(ROI)Dang An Binh?,Hirotaka Shimada?,Takao Kanzaki?,Arifudin Achmad?,Takahito Nakajima?,Tetsuya Higuchi??and Yoshito Tsushima?（１ Department of Diagnostic Radiology and Nuclear Medicine,Gunma Univer-sity Graduate School of Medicine）（２ Department of Radiology,Gunma Uni-versity Hospital）【Purpose】 To check the performance of diferent aorta’s region of interest(ROIs)on mean cerebral blood flow(mCBF)value when using Patlak plot graphical analysis in― ―248第63回北関東医学会総会

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Mechanisms of ATP-induced IL-6 Production in Systemic Sclerosis Fibroblasts

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