Role of stress proteins (HSP65) and dendritic cells in inflammatory skin diseases

应激蛋白（HSP65）和树突状细胞在炎症性皮肤病中的作用

• 批准号: 06670877
• 负责人: IZAKI Seiichi
• 金额: $ 1.34万
• 依托单位: Saitama Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670877/
• 关键词: stress protein; heat shock; HSP65; focal infection; psoriasis; palmoplantar pustulosis; dendritic cells; thrombomodulin; 乾樹; 学蹠膿疱症; トロンボ モジュリン; ブドウ球菌; 連鎖球菌; スタフィロキナーゼ

Chronic and latent infectious focus in a distant part of the body may trigger diverse inflammatory disorders in the skin. It has been interpreted as "focal infection" without explainion of the precise mechanism. We noticed that this process includes various interesting subjects, that lead us to the present projict. Immunogenetically well-conserved stress proteins or heat shock proteins (HSPs), are considered to be induced in both parasitic microorganisms and infected host humans.This may result in host-defense to bacteria and, on the other hand, occasional induction of immunomodulation, since bacterial HSPs are highly immunogenic and targetted by immune surveilance of hosts, while mammalian HSPs indued after infectious stress are able to be recognized by the same immune mechanism of the host. We have investigated antibody level to mycobacterial HSP65 with ELISA technique in various inflammatory skin dieases in order to correlate this with so-called "focal infection". In comparison to n … More ormal group, patients with palmoplanter pustulosis, psoriasis, urticaria, and herpes zoster showed elevated IgG antibody level to HSP65 from Mycobacterium leprae. Among patients with psoriasis acute guttate psoriasis showed significant increase in anti-HSP65 IgG,while psoriasis vulgaris and psoriasis pustulosa showed no significant increase. Among patients with palmoplantar pustulosis, patients with infectious focus showed significant increase in anti-HSP65 IgG,compared to those without it.We further investigated antibody level to staphylokinase, that is antigenic and fibrinolytic protein produced and secreted by infectious Staphylococcus aureus, in patients with the skin disorders. We found that anti-staphylokinase is a useful indicator of staphylococcal infection, and an independent parameter from ASLO and ASK,that are indicators of streptococcal infection.Patients with psoriasis and palmoplantar pustulosis associated with infectious foci showed significant increase in anti-staphylokinase IgG.Recently we immunohistochemically investigated dermal dendritic cells with markers such as Factor XIIIa, Thrombomodulin, and CD34. Each marker showed unique cell population and distribute in the inflamed skin tissue. Biological significance of those dendritic cells in relation to mononuclear phagocytes are now under investigation. Less

身体远处的慢性和潜伏性感染病灶可能引发皮肤中的各种炎症性疾病。它被解释为“局灶性感染”，但没有解释确切的机制。我们注意到，这个过程包括各种有趣的主题，导致我们目前的项目。热休克蛋白（heat shock protein，HSPs）是一种高度保守的免疫应激蛋白，在寄生微生物和感染的宿主体内均可被诱导产生，这一方面可导致宿主对细菌的防御，另一方面，由于细菌的热休克蛋白具有高度免疫原性，可被宿主的免疫监视所靶向，因此有时也可诱导免疫调节。而哺乳动物感染应激后诱导的HSPs能被宿主相同的免疫机制识别。我们用ELISA技术检测了各种炎症性皮肤病中抗分枝杆菌HSP65抗体水平，以便将其与所谓的“局灶性感染”联系起来。与n相比 ...更多信息 正常对照组掌跖脓疱病、银屑病、荨麻疹、带状疱疹患者血清中抗麻风杆菌HSP 65 IgG抗体水平明显升高。在银屑病患者中，急性点滴状银屑病患者的抗HSP 65 IgG显著升高，而寻常型银屑病和脓疱型银屑病患者的抗HSP 65 IgG无显著升高。在掌跖脓疱病患者中，有感染灶的患者抗HSP 65 IgG水平显著高于无感染灶的患者。我们进一步研究了皮肤病患者对葡激酶（由感染性金黄色葡萄球菌产生和分泌的抗原性和纤溶蛋白）的抗体水平。我们发现，抗葡激酶是葡萄球菌感染的一个有用的指标，并从ASLO和ASK，这是链球菌感染的指标的一个独立的参数。银屑病和掌跖脓疱病与感染focus.Recently相关的患者表现出显着增加抗葡激酶IgG。我们化学研究了真皮树突状细胞与标记物，如因子XIIIa，血栓调节蛋白，和CD 34。每种标记物显示独特的细胞群并分布在发炎的皮肤组织中。这些树突状细胞与单核吞噬细胞相关的生物学意义正在研究中。少

项目成果

Izaki S,Goto Y,Kaburagi Y,Kitamura K,Nomaguchi H.: "Antibody production to heat shock proteins with Mr65kD(HSP65)in cutaneous inflammation:A possible relationship to focal infection." Acta Ctolaryngol. (in press). (1996)

Izaki S、Goto Y、Kaburagi Y、Kitamura K、Nomaguchi H.：“皮肤炎症中 Mr65kD (HSP65) 热休克蛋白的抗体产生：与病灶感染的可能关系。”

IZAKIS,GOTO Y,KABURAGI Y,KITAMURA K,MOMAGUCHI H.: Excerpta Medica, Amsterdam.Heat shock (stress) proteins and potential immunomodullatory activity. In : Pediatric Dermatology (ICS1073), (eds) Pierini AM,DePierini GD,Bustamante RE., 287-292 (1995)

IZAKIS，GOTO Y，KABURAGI Y，KITAMURA K，MOMAGUCHI H.：医学摘录，阿姆斯特丹。热休克（应激）蛋白和潜在的免疫调节活性。

飯泉陽子,黒崎百合子,伊崎誠一,他: "顔面播種状粟粒性狼瘡の免疫組織化学的研究:慢性肉芽腫性炎症におけるトロンボジュリン陽性浸潤細胞について" 日皮会雑誌. 104. 589-593 (1994)

Yoko Iizumi、Yuriko Kurosaki、Seiichi Izaki 等：“面部播散性粟粒性狼疮的免疫组织化学研究：慢性肉芽肿性炎症中血栓调节蛋白阳性浸润细胞”日本皮肤病学会杂志 104. 589-593 (1994))。

飯泉陽子,伊崎誠一,北村啓次郎,丸山征郎: "炎症浸潤細胞のトロンボモジュリン(TM):皮膚サルコイドーシスの免疫組織化学的研究から" 血栓止血誌. 5. 275-282 (1994)

Yoko Iizumi、Seiichi Izaki、Keijiro Kitamura、Seiji Maruyama：“炎症浸润细胞中的血栓调节蛋白 (TM)：皮肤结节病的免疫组织化学研究”《血栓形成与止血杂志》5. 275-282 (1994)。

IZAKI S,GOTO Y.KITAMURA K,NOMAGUCHI H.: "Antibody to 65-kD stress protein (HSP65) of Mycobacterium leprae in various inflammatory skin diseases : A preliminary report." Jpn J Leprosy. 63. 3-11 (1994)

IZAKI S、GOTO Y.KITAMURA K、NOMAGUCHI H.：“各种炎症性皮肤病中麻风分枝杆菌 65-kD 应激蛋白 (HSP65) 的抗体：初步报告。”