REGULATION OF CYTOKINE GENE EXPRESSION IN MAST CELLS

肥大细胞中细胞因子基因表达的调节

• 批准号: 6098983
• 负责人: Dean D Metcalfe
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6098983
• 关键词: cytokine; gene expression; genetic library; genetic transcription; human genetic material tag; human tissue; laboratory mouse; mast cell; molecular cloning; northern blottings; tissue /cell culture

It is known that rodent mast cells respond to nerve growth factor (NGF). We have now shown that both the human mast cell line HMC-1 and cultured human mast cells similarly respond to NGF as evidenced by induction of the immediate early gene c-fos through the trkA tyrosine receptor which is phosphorylated on tyrosine residues following NGF exposure. HMC-1 and human mast cells were also found to express NGF mRNA and conditioned media from HMC-1 cells stimulated neurite outgrowth, an effect blocked by anti-NGF. Similarly, we identified the receptor for alpha-melanocyte stimulating hormone (alpha-MSH), MC-1, on murine mast cells. Treatment of mast cells with alpha-MSH increased cAMP levels and down-modulated expression of mRNA for IL-1beta, TNF-alpha, and lymphotactin in activated mast cells. In an animal model of asthma, we have characterized the resident cells responsible for immediate-early IL-4 production following antigen challenge.

众所周知，啮齿动物肥大细胞对神经有反应 生长因子（NGF）。我们现在已经表明了两个人 肥大细胞系HMC-1和培养的人类肥大细胞类似 响应NGF，这可以通过诱导立即诱导 通过TRKA酪氨酸受体的基因C-FOS是 NGF暴露后，磷酸化在酪氨酸残基上。 还发现HMC-1和人类肥大细胞表达NGF 来自HMC-1细胞的mRNA和条件培养基刺激了神经突 出生，抗NGF阻塞的效果。同样，我们确定了 α-核细胞刺激激素的受体 （α-MSH），MC-1，在鼠肥大细胞上。肥大细胞的处理 随着Alpha-MSH的增加，营地水平增加并进行了下调 在IL-1Beta，TNF-Alpha和淋巴结蛋白中的mRNA表达 活化的肥大细胞。在哮喘的动物模型中，我们有 表征了负责立即IL-4的居民细胞 抗原挑战后的生产。