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.

已知啮齿动物的肥大细胞对神经有反应 生长因子(NGF)。我们现在已经证明，人类 肥大细胞系HMC-1与培养的人肥大细胞相似 对NGF的反应表现为诱导即刻早期 通过TrkA酪氨酸受体表达c-fos基因 在NGF暴露后，酪氨酸残基被磷酸化。 HMC-1和人类肥大细胞也表达NGF HMC-1细胞刺激神经突起的mRNA和条件培养液 生长，一种被抗NGF阻断的作用。同样，我们发现 α-黑素细胞刺激素受体 (Alpha-MSH)，MC-1，小鼠肥大细胞。肥大细胞的治疗 随着α-MSH水平升高和cAMP水平下调 白介素1β、肿瘤坏死因子-α和淋巴动蛋白的mRNA表达 激活的肥大细胞。在哮喘的动物模型中，我们有 表征了负责即刻早期IL-4的驻留细胞 在抗原挑战后产生。