IL-32及其触发的细胞因子网络在多发性骨髓瘤发生发展中的作用及机制研究

多发性骨髓瘤（MM）是起源于B细胞系的恶性血液系统疾病，其发生发展主要取决骨髓微环境和细胞内部的基因不稳定性。炎性细胞及炎症因子作为骨髓微环境的组成部分，可通过诱导基因不稳定性促进MM发生发展。我们的前期研究发现，MM患者血清促炎性因子IL-32水平明显增高，后者是炎症反应“级联放大效应” 的关键因子之一，促进骨髓基质细胞分泌IL-6等炎性因子；而IL-6是 MM 细胞增殖最重要的细胞因子，与MM的发病密切相关。本课题拟采用细胞学、免疫学、分子生物学、动物实验等方法，在体内外研究IL-32及其触发的IL-6等因子分泌的作用及其具体机制，观察IL-32作用下细胞因子网络的改变以及该网络中各炎性因子对MM细胞基因不稳定性、细胞增殖的作用和分子机制；旨在阐明炎性因子网络在MM疾病病理机制中的作用，为早期干预MM发生、发展提供理论基础，为进一步设计新的靶向治疗策略提供实验依据。

Multiple myeloma (MM) is a malignant blood system disease which originates from the B cell lineage, its development mainly depends on the bone marrow microenvironment and genetic instability of the cells. Inflammatory cells and inflammatory factors, as parts of the bone marrow microenvironment, can promote the occurrence and development of MM by inducing genetic instability. We have found elevated serum levels of inflammatory factors IL-32 in MM patients, the latter is one of the key factors in inflammation ‘cascade amplification effect’ promoting secretion of inflammatory factors such as IL-6 by a variety immune cells. IL-6 is the most important cytokine in MM cell proliferation, closely related to the occurrence of MM. We propose cytology, immunology, molecular biology methods and animal experiment, to study the role and specific mechanism of IL-6 and other inflammatory factors triggered by IL-32 in vivo and vitro, to further observe the change of cytokine network under the action of IL-32, to find the effect of inflammatory cytokines in MM cell genetic instability and proliferation, apoptosis, drug resistance and their molecular mechanism. To clarify the role of inflammatory factor network in MM disease pathological mechanism, providing theoretical and experimental basis for early intervention and further new targeted therapeutic strategies of MM.