Mechanisms of immune responses by toll-like receptor against Infection and organ failure

Toll样受体针对感染和器官衰竭的免疫反应机制

• 批准号: 13671232
• 负责人: NISHIDA Toshirou
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671232/
• 关键词: Surgical insult; Endotoxin; Toll-like receptor; Cytokine production; Innate immunity; Immunosuppression; Infection; Organ failure; 敗血症; till-like receptors; interleukin-6; TNFα; 外科侵襲; 感染症

Although surgical insults may induce postoperative immunosuppression, its mechanism remains unknown. The aim of this study was to examine TLR2 and TLR4 expression on monocytes and their responses to each agonist after surgical insults. The subjects were patients who received gastrointestinal surgery. Peripheral blood mononuclear cells (PBMC) at the indicated times were extracted from the patients and their TLR2, TLR4 and inducible nitric oxide synthase (iNOS) expressions were analyzed. TLR2 and TLR4 were rapidly decreased and showed lowest values on the 1st and 3rd postoperative days, respectively. Next, we measured Macrophage-activating lipopeptide-2 (MALP-2)- or lipopolysaccharide (LPS)- induced TNF- α and IL-6 production. MALP-2-stimulated TNF- α and IL-6 production was significantly decreased after surgery and increased to a maximum value on the 1st postoperative day, then gradually decreased. LPS-stimulated TNF- α production was significantly suppressed after surgery then showed a gradual increase to maximum values on the 3rd postoperative day. iNOS in PBMC was significantly induced after surgery. In conclusion, expression of TLR2 and TLR4 was down-regulated by surgery, and agonist-induced cytokine production was transiently suppressed and soon increased through activation of PBMC. The present study may offer new insights for postoperative modulation of innate immunity under surgical stress.

虽然手术损伤可引起术后免疫抑制，但其机制尚不清楚。本研究的目的是检查TLR 2和TLR 4的表达单核细胞和他们的反应，每一个激动剂手术损伤后。受试者为接受胃肠道手术的患者。在指定的时间点从患者中提取外周血单个核细胞（PBMC）并分析其TLR 2、TLR 4和诱导型一氧化氮合酶（iNOS）的表达。TLR 2和TLR 4迅速下降，分别在术后第1天和第3天达到最低值。接下来，我们测量了巨噬细胞活化脂肽-2（MALP-2）或脂多糖（LPS）诱导的TNF- α和IL-6的产生。MALP-2刺激的TNF- α和IL-6的产生在手术后显著降低，并在术后第1天增加到最大值，然后逐渐降低。LPS刺激的TNF- α产生在手术后被显著抑制，然后在术后第3天逐渐增加至最大值。术后PBMC中iNOS表达明显增加。总之，TLR 2和TLR 4的表达被手术下调，激动剂诱导的细胞因子产生被短暂抑制，并很快通过激活PBMC而增加。本研究可能为手术应激下先天免疫的术后调节提供新的见解。

项目成果

Nishida T, Kumano S, Sugiura T, Ikushima H, Nishikawa, K Ito T, Matsuda H.: "Potential Use of CT in Evaluation for Occult Gastrointestinal Stromal Tumors in High Risk Patients."Am J Roentogenol. 180(1). 185-189 (2003)

Nishida T、Kumano S、Sugiura T、Ikushima H、Nishikawa、K Ito T、Matsuda H.：“CT 在高危患者隐匿性胃肠道间质瘤评估中的潜在用途。”Am J Roentogenol。

Nishida T, Katayama S, Tsujimoto M.: "Histological Vascular Invasion of Differentiated Thyroid Carcinoma and its Clinicopathological Significance."Am J Surg. 183(1). 80-86 (2002)

Nishida T、Katayama S、Tsujimoto M.：“分化型甲状腺癌的组织学血管侵袭及其临床病理学意义。”Am J Surg。

Nishikawa K, Kawahara H, Yumiba T, Nishida T, Inoue Y, Ito T, Matsuda H.: "Functional characteristics of the pylorus-preserving gastrectomy br early gastric cancer"Surgery. 131(6). 613-624 (2002)

Nishikawa K、Kawahara H、Yumiba T、Nishida T、Inoue Y、Ito T、Matsuda H.：“早期胃癌保留幽门胃切除术的功能特征”手术。

Nishida T, Mizushima T, Kitagawa T, Ito T, Sugiura T, Matsuda H.: "Unusual Type of Left Paraduodenal Hernia Caused by Separated Peritoneal."J Gastroenterology. 37. 742-744 (2002)

Nishida T、Mizushima T、Kitakawa T、Ito T、Sugiura T、Matsuda H.：“由腹膜分离引起的左侧十二指肠旁疝的异常类型。”J Gastroenterology。

Nishida T, Fujita N, Megawa T, Nakahara M, Nakao K.: "Postoperative Hyperbilirubinemia alter Surgery for Gastrointestinal Perforation"Surgery Today. 32. 679-684 (2002)

Nishida T、Fujita N、Mekawa T、Nakahara M、Nakao K.：“术后高胆红素血症改变胃肠穿孔手术”今日外科。