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两性霉素B可诱导人单核细胞系THP-1中编码趋化因子和细胞黏附分子的基因表达。

Amphotericin B induces expression of genes encoding chemokines and cell adhesion molecules in the human monocytic cell line THP-1.

作者信息

Rogers P D, Stiles J K, Chapman S W, Cleary J D

机构信息

Dept. of Clinical Pharmacy Practice, School of Pharmacy, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.

出版信息

J Infect Dis. 2000 Oct;182(4):1280-3. doi: 10.1086/315835. Epub 2000 Aug 28.

DOI:10.1086/315835
PMID:10979935
Abstract

Amphotericin B is known to elicit immunomodulatory effects on neutrophil, monocyte, and lymphocyte function. It also has been shown to induce the release of proinflammatory cytokines from human monocytes and macrophages. Release of these cytokines has been associated with the infusion-related toxicity observed after administration of this drug. The present study demonstrates that amphotericin B increases mRNA for the chemokines interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1beta, as well as the cell adhesion molecules intercellular adhesion molecule (ICAM)-1 and CD44 in the human monocytic cell line THP-1. Amphotericin B increased the concentrations of IL-8, MCP-1, and MIP-1beta in a dose-dependent fashion. Amphotericin B also induced expression of ICAM-1 but not CD44 in these cells. Production of these proteins in response to amphotericin B may play a role in the immunomodulatory activity and toxicity of this antifungal agent.

摘要

两性霉素B已知对中性粒细胞、单核细胞和淋巴细胞功能具有免疫调节作用。它还被证明可诱导人单核细胞和巨噬细胞释放促炎细胞因子。这些细胞因子的释放与该药物给药后观察到的输液相关毒性有关。本研究表明,两性霉素B可增加人单核细胞系THP-1中趋化因子白细胞介素(IL)-8、单核细胞趋化蛋白(MCP)-1和巨噬细胞炎性蛋白(MIP)-1β的mRNA水平,以及细胞黏附分子细胞间黏附分子(ICAM)-1和CD44的mRNA水平。两性霉素B以剂量依赖方式增加IL-8、MCP-1和MIP-1β的浓度。两性霉素B还诱导这些细胞中ICAM-1的表达,但不诱导CD44的表达。响应两性霉素B产生这些蛋白质可能在这种抗真菌剂的免疫调节活性和毒性中起作用。

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