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，啮齿类动物的肥大细胞会对神经元产生反应， 生长因子（NGF）。我们现在已经证明， 肥大细胞系HMC-1和培养的人肥大细胞类似地 对NGF的反应，如通过诱导即刻早期 基因c-fos通过trkA酪氨酸受体， 在NGF暴露后酪氨酸残基上磷酸化。 HMC-1和人肥大细胞也表达NGF HMC-1细胞的mRNA和条件培养基刺激神经突 生长，抗神经生长因子阻断的效果。同样，我们发现 α-黑素细胞刺激激素受体 （α-MSH），MC-1，对鼠肥大细胞的作用。肥大细胞的治疗 与α-MSH增加cAMP水平和下调 IL-1 β、TNF-α和巨噬细胞趋化因子mRNA表达 激活的肥大细胞在哮喘的动物模型中， 表征了负责立即早期IL-4的驻留细胞， 抗原攻击后的生产。