REG OF THE NADPH OXIDASE BY ANTI-INFLAMMATORY AGENTS

抗炎药对 NADPH 氧化酶的调节

• 批准号: 6394921
• 负责人: PETER E NEWBURGER
• 金额: $ 4.03万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6394921
• 关键词: NAD(P)H dehydrogenase; antiinflammatory agents; cell differentiation; colony stimulating factor; cooperative study; cytochrome b; enzyme activity; enzyme inhibitors; gene expression; genetic regulation; glucocorticoids; interferon gamma; messenger RNA; monocyte; nonsteroidal antiinflammatory agent; phagocytes; superoxides; tissue /cell culture; transcription factor; tumor necrosis factor alpha

The long-term goal of this project will be to investigate the regulation of the superoxide-generating NADPH oxidase of phagocytic leukocytes. Oxygen species generated by this enzyme system play a major role in host defense against infection and as well as in tissue damage during inflammation and reperfusion injury. Our work will focus on the cytochrome b component of the NADPH oxidase, in particular the gene encoding gp91-phox, the 91 kilodalton glycoprotein of the phagocyte cytochrome b heterodimer. Expression of this and closely related genes is developmentally regulated and virtually lineage-specific to myelomonocytic cells. Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAID) modulate the expression of various genes and cell functions. The proposed studies will test the central hypothesis that glucocorticoids and NSAID inhibit phagocytic NADH oxydase activity by down-regulating expression of genes encoding components of the NADPH oxidase system. We will: 1. Develop a system for the differentiation of the human monocytic cell line THP-1 by cytokines that influence phagocyte function: We will examine the NADPH oxidase activity, cytochrome b content, and expression of the genes encoding gp91-phox and the other NADPH oxidase components. 2. Study the effects of glucocorticoids and NSAID on the NADPH oxidase system of cytokine-differentiated THP-1 cells: We will examine the effect of glucocorticoids and NSAID on the NADPH oxidase activity, cytochrome b content, and expression of the genes encoding gp91-phox and the other NADPH oxidase components. 3. Investigate the effects of cytokines, glucocorticoids or NSAID on the regulation of the NADPH oxidase system in human peripheral blood monocytes/macrophages: We will investigate the effects of glucocorticoids or NSAID on the NADPH oxidase activity, cytochrome b content, and expression of the genes encoding gp91-phox and the other NADPH oxidase components in human peripheral blood monocytes/macrophages under cytokine stimulation. The proposed studies should advance our fundamental knowledge of transcriptional control mechanisms in the myelomonocytic lineage and as well determine new mechanisms by which anti-inflammatory agents exert their anti-inflammatory effects, in this case by down-regulating the expression of genes encoding components of the phagocytic NADPH oxidase system. Better understanding of the pharmacological regulation of the NADPH oxidase system will provide information to help modulate its expression during inflammation and oxidant-mediated tissue damage.

该项目的长期目标是研究吞噬白细胞的超氧化物生成氧化氧化酶的调节。 该酶系统产生的氧气在宿主防御感染以及炎症和再灌注损伤期间以及组织损伤中起着重要作用。 我们的工作将集中在NADPH氧化酶的细胞色素B成分上，特别是编码GP91-PHOX的基因，GP91-PHOX是吞噬细胞细胞色素B异二聚体的91千洛达尔顿糖蛋白。 该基因和密切相关的基因的表达在发育中受到调节，并且对脊髓细胞细胞几乎特异性谱系。 糖皮质激素和非甾体类抗炎药（NSAID）调节各种基因和细胞功能的表达。 拟议的研究将检验中心假设，即糖皮质激素和NSAID通过下调编码NADPH氧化酶系统的基因的表达来抑制吞噬NADH氧酶的活性。 我们将：1。开发一个通过影响吞噬细胞功能的细胞因子来区分人类单核细胞系THP-1的系统：我们将检查编码GP91-PHOX和其他NADPHPHPHEXIDASE CONEMENT的NADPH氧化酶活性，细胞色素B含量以及编码GP91-PHOX的基因的表达。 2。研究糖皮质激素和NSAID对细胞因子分化的THP-1细胞NADPH氧化酶系统的影响：我们将研究糖皮质激素和NSAID对NADPH氧化酶活性，细胞色素B含量以及编码GP91-Phox和其他NADPHASES Compase compase compose componease compose compose compone的基因表达的NADPH氧化酶活性的影响。 3。研究细胞因子，糖皮质激素或NSAID对人外周血单核细胞/巨噬细胞中NADPH氧化酶体系调节的影响：我们将研究糖皮质激素或NSAID对NADPH氧化酶活性，细胞与氧化物B含量的糖皮质激素或NSAID对基因的NADPH氧化酶活性的影响。细胞因子刺激下的外周血单核细胞/巨噬细胞。拟议的研究应提高我们对脊髓细胞谱系中转录控制机制的基本知识，并确定抗炎剂施加抗炎作用的新机制，在这种情况下，通过下调编码吞噬非腺细胞氧化酶体系的基因表达来表达。 更好地了解NADPH氧化酶系统的药理调节将提供信息，以帮助调节其在炎症和氧化剂介导的组织损伤过程中的表达。

项目成果

[Autosomal chronic granulomatous disease: case report and mutation analysis of two Brazilian siblings].

常染色体慢性肉芽肿病：巴西两兄妹病例报告及突变分析。

• 发表时间: 2004
• 期刊: Jornal de pediatria
• 影响因子: 3.3
• 作者: Prando-Andrade,Carolina;Agudelo-Florez,Piedad;Lopez,JuanA;Paiva,MariaAparecidadeSouza;Costa-Carvalho,BeatrizT;Condino-Neto,Antônio
• 通讯作者: Condino-Neto,Antônio

The use of reverse transcription-PCR for the diagnosis of X-linked chronic granulomatous disease.

使用逆转录 PCR 诊断 X 连锁慢性肉芽肿病。

• DOI: 10.1590/s0100-879x2004000500001
• 发表时间: 2004
• 期刊: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
• 作者: Agudelo-Flórez,P;López,JA;Redher,J;Carneiro-Sampaio,MMS;Costa-Carvalho,BT;Grumach,AS;Condino-Neto,A
• 通讯作者: Condino-Neto,A