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白细胞介素-18对口腔鳞状细胞癌患者白细胞中诱导型一氧化氮合酶及磷酸化核因子-κB抑制蛋白表达的影响

Effect of IL-18 on leukocyte expression of iNOS and phospho-IkB in patients with squamous cell carcinoma of the oral cavity.

作者信息

Jabłońska E, Puźewska W, Charkiewicz M

机构信息

Department of Immunology, Medical University of Bialystok, 15-274 Bialystok, Poland.

出版信息

Neoplasma. 2006;53(3):200-5.

PMID:16652188
Abstract

The inducible synthase of nitric oxide (iNOS) is responsible for the synthesis of nitric oxide (NO) in neutrophils (PMN) and in peripheral blood mononuclear cells (PBMC). This enzyme is controlled by a number of cytokines which accomplish their biological effect via e.g. activation of NF-kB pathway. The aim of the present study was to assess the expression of iNOS and production of NO by PMN and PBMC in patients with oral cavity squamous cell carcinoma (SCC), and to examine the role of the NF-kB pathway in the IL-18-stimulated activation of this enzyme. The production of NO and iNOS expression in PMN were reduced, while iNOS expression in PBMC was increased but NO production by these cells remain unchanged. Patients after treatment showed lower intensity of iNOS expression compared to that observed before treatment. Moreover, both before and after treatment iNOS expression was inversely correlated with phospho-IkB expression in PMN and in PBMC. Significantly higher levels of total NO were observed in the serum of Stage IV patients before and after treatment as compared to the control group. Altered expression of iNOS and NO generation by PMN and PBMC may have an unfavorable effect on the course of antineoplastic response in patients with squamous cell carcinoma of the oral cavity. Intensification of iNOS expression and NO production in Stage IV patients, induced by rhIL-18, suggests its beneficial effect on the activity of leukocytes in patients with squamous cell carcinoma of the oral cavity.

摘要

诱导型一氧化氮合酶(iNOS)负责在中性粒细胞(PMN)和外周血单核细胞(PBMC)中合成一氧化氮(NO)。该酶受多种细胞因子调控,这些细胞因子通过例如激活NF-κB途径来实现其生物学效应。本研究的目的是评估口腔鳞状细胞癌(SCC)患者中PMN和PBMC的iNOS表达及NO生成,并研究NF-κB途径在IL-18刺激该酶激活过程中的作用。PMN中NO的生成及iNOS表达降低,而PBMC中iNOS表达增加,但这些细胞的NO生成保持不变。治疗后的患者与治疗前相比,iNOS表达强度较低。此外,治疗前后PMN和PBMC中iNOS表达均与磷酸化IκB表达呈负相关。与对照组相比,IV期患者治疗前后血清中总NO水平显著更高。PMN和PBMC中iNOS表达及NO生成的改变可能对口腔鳞状细胞癌患者的抗肿瘤反应进程产生不利影响。重组人白细胞介素-18(rhIL-18)诱导IV期患者iNOS表达和NO生成增强,提示其对口腔鳞状细胞癌患者白细胞活性具有有益作用。

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TRAIL-Expressing Monocyte/Macrophages Are Critical for Reducing Inflammation and Atherosclerosis.表达肿瘤坏死因子相关凋亡诱导配体(TRAIL)的单核细胞/巨噬细胞对减轻炎症和动脉粥样硬化至关重要。
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