MOLECULAR REGULATION OF INTERLEUKIN 12 GENE EXPRESSION

白介素12是一种关键的细胞因子，代表着 一种有效的宿主免疫防御的细胞和体液分支 仪器。它是诱导T细胞依赖的一个关键因素。 巨噬细胞的独立激活，T细胞的产生有助于1型和 细胞毒性T细胞、对细菌和寄生虫感染的抵抗力以及 消除肿瘤。IL-12是由两个亚基组成的杂二聚体， 编码在不同人类染色体上的p40和p35。这个 这两个基因的表达是高度协调的，形成了 在有效免疫反应期间具有生物活性的IL-12。然而， 在某些病理条件下，IL-12调节失调，导致 要么是缺乏对微生物感染的抵抗力，要么是不受控制 肿瘤生长，或在破坏性炎症中。我们假设一个 IL-12产生的暂时性或不可逆性失调反映了 病原体/肿瘤细胞诱导的高度协调的破坏 P40和p35基因的表达。这项建议旨在：(一) 鉴定和鉴定可激活的转录因子 激活IL-12 p40基因表达的因子 致病刺激；(2)探讨其分子机制。 致病刺激对IL-12 p40基因表达的影响 探讨T细胞IL-12 p40基因表达的分子机制， B细胞和单核细胞；(3)抑制的分子基础分析 免疫抑制剂对IL-12基因表达的影响。理解 调控IL-12p40和IL-12p40表达的分子机制 P35基因在病原菌与细菌相互作用中的作用 免疫系统将对我们的设计工作大有裨益 治疗传染病和恶性疾病的治疗策略。

Interleukin-12 is a pivotal cytokine representing the link between the cellular and humoral branches of an effective host immune defense apparatus. It is a key factor in the induction of T-cell dependent and independent activation of macrophages, generation of T helped type 1 and cytotoxic T cells, resistance to bacterial and parasitic infections, and elimination of tumors. IL-12 is a heterodimer consisted to two subunits, p40 and p35 that are encoded on different human chromosomes. The expression of these two genes are highly coordinated to form the biologically active IL-12 during an effective immune response. However, under some pathological conditions IL-12 is dysregulated, resulting either in a lack of resistance to microbial infection and uncontrolled tumor growth, or in destructive inflammation. We hypothesize that a transient or irreversible dysregulation of IL-12 production reflects a pathogen/tumor cell-induced disruption in the highly coordinated expression of p40 and p35 genes. This proposal is aimed at: (1) identifying and characterizing the transcription factors which activate factors which activate IL-12 p40 gene expression in response to pathogenic stimulation; (2) investigating the molecular mechanisms of IL-12 p40 gene expression in response to pathogenic stimulation; (2) investigating the molecular mechanism of IL-12 p40 gene expression in T, B and monocytic cells; (3) analyzing the molecular basis of inhibition of IL-12 gene expression by immunosuppressive agents. The understanding of the molecular mechanisms governing the expression of IL-12 p40 and p35 genes in the context of interactions between pathogens and the immune system will benefit significantly our efforts in designing therapeutic strategies to treat infectious and malignant diseases.