Role of IL-18 in Tissue Destruction and Compensatory Reactions in Mucosal Tissue of Nematode Infected Mice

IL-18在线虫感染小鼠粘膜组织破坏和代偿反应中的作用

• 批准号: 14570226
• 负责人: KASHIWAMURA Shin-ichiro
• 金额: $ 1.79万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570226/
• 关键词: Mucosal Immunity; Inflammation; IL-18; IL-12; Prostaglandin; Gland; Tissue Damage; Compensatory Reaction; 組織障害

IL-18 was recognized as a pro-inflammatory cytokine, which played important roles for induction of NO,ROI and TNF-α, via the production of IFN-γ with IL-12. Those factors were required for elimination of infectious microbes(Singh R.P., et al., J.Immunol.,2003), while those caused tissue damages(Shimmyo A.K., et al., J.Immunothera.,2002). However, in recent studies, we had revealed that IL-18 also carried the capability to induce anti-inflammatory cytokines, such as IL-4,IL-10 and IL-13 from T cells, NK cells and mast cells, in the absence of IL-12(Kashiwamura S., et al., J.Immunothera.,2002 ). In these studies, we had discussed new physiological roles of IL-18. When IL-18 was administered to mice with IL-12, this treatment caused liver steatosis by the impairment of micro circulation in the liver with induced excess NO(Kaneda M., et al., J.Interferon Cytokine Res.,2003). Further, it became clear that, the IL-18 concentration in the circulation highly related to the risk of myocardial infarction(Kawasaki D., et al., Am.J.Cardiol.,2003). High concentration of IL-18 was also observed in peritoneal fluid of the patients of endometriosis(Oku H., et al., Hum.Reprod.2004). In this study, we discovered that, IL-18 receptor was expressed in non-immune parenchymal cells in mucosal tissue, while IL-18 was expressed in infiltrating macrophages. Which implicated that, these parenchymal cells expressed COX-2 gene to produce PGE2 and suppressed inflammatory cytokines such as TNF-α, in response to IL-18.

IL-18 被认为是一种促炎细胞因子，通过与 IL-12 一起产生 IFN-γ，在诱导 NO、ROI 和 TNF-α 方面发挥重要作用，这些因子是消除感染性微生物所必需的（Singh）。 R.P., et al., J.Immunol.,2003)，而那些会造成组织损伤(Shimmyo A.K., et al., J.Immunothera.,2002)。然而，在最近的研究中，我们发现IL-18还具有从T细胞、NK细胞和肥大细胞诱导抗炎细胞因子的能力，例如IL-4、IL-10和IL-13。 IL-12 (Kashiwamura S., et al., J.Immunothera.,2002) 在这些研究中，我们讨论了当将 IL-18 给予具有 IL-12 的小鼠时，IL-18 的新生理作用。这种治疗通过诱导过量的NO而损害肝脏中的微循环而引起肝脏脂肪变性(Kaneda M.等人，J.Interferon Cytokine Res.，2003)。此外，清楚的是，IL-18浓度在肝脏中增加。血液循环与心肌梗塞的风险高度相关（Kawasaki D., et al., Am.J.Cardiol.,2003）。子宫内膜异位症患者的腹腔液(Oku H., et al., Hum.Reprod.2004)在本研究中，我们发现，IL-18受体在粘膜组织的非免疫实质细胞中表达，而IL-18受体在粘膜组织中的非免疫实质细胞中表达。 18在浸润巨噬细胞中表达，这表明这些实质细胞表达COX-2基因以产生PGE2并抑制炎症细胞因子，例如TNF-α，对 IL-18 的反应。

项目成果

Hosohara, K.: "Interleukin-18 induces acute biphasic reduction in the levels of circulating leukocytes in mice"Clinical and Diagnostic Laboratory Immunology. 9. 777-783 (2002)

Hosohara, K.：“Interleukin-18 诱导小鼠循环白细胞水平急性双相降低”临床和诊断实验室免疫学。

Kashiwamura S., et al.: "Roles of Interleukin-18 in Tissue Destruction and Compensatory Reactions."J.Immunothera.. 25(suppl.1). S4-S11 (2002)

Kashiwamura S. 等人：“Interleukin-18 在组织破坏和补偿反应中的作用”。J.Immunothera.. 25（增刊 1）。

Katsushi Hosohara, Haruyasu Ueda, Shin-Ichiro Kashiwmaura, Takako Yano, Takeharu Ogura, Seishiro Marukawa, Haruki Okamura: "Interleukin-18 Induces Acute Biphasic Reduction in the Levels of Circulating Leukocytes in Mice."Clinical and Diagnostic Laboratory

Katsushi Hosohara、Haruyasu Ueda、Shin-Ichiro Kashiwmaura、Takako Yano、Takeharu Ogura、Seishiro Marukawa、Haruki Okamura：“Interleukin-18 诱导小鼠循环白细胞水平急性双相降低。”临床和诊断实验室

Kokai M., et al.: "Plasma Interleukin-18 Levels in Patients Wiyh Psychiatric Disorders."J.Immunothera.. 25(suppl.1). S68-S71 (2002)

Kokai M. 等人：“患有精神疾病的患者血浆白细胞介素 18 水平。”J.Immunothera.. 25(suppl.1)。

Iwasaki, T.: "Interleukin-18 inhibits osteolytic bone metastasis by human lung cancer cells possibly through suppression of osteoclastic bone-resorption in nude mice"Journal of Immunotherapy. Suppl.-1. 52-60 (2002)

Iwasaki, T.：“Interleukin-18 可能通过抑制裸鼠破骨细胞骨吸收来抑制人肺癌细胞溶骨性骨转移”《免疫治疗杂志》。