miR-183/ALOX15信号通路调控促炎症消退介质在银屑病中的作用及机制研究

银屑病的病理基础是中性粒细胞趋化、角质形成细胞（KC）异常增殖以及淋巴细胞分化失衡，这与促炎症消退介质（脂氧素和消退素等）的抗炎促消退效应很好的对应，并已证实其能抑制银屑病发病。我们发现银屑病皮损区促炎症消退介质和及其关键酶ALOX15表达均明显下降。有报道，人银屑病皮损中miR-183明显上调，我们前期也发现脂多糖活化的KC中，miR-183表达显著升高，且KC增殖加强。通过基因序列对比发现 ALOX15的3’-UTR区存在miR-183的结合位点。我们提出假想，miR-183可通过ALOX15调控促炎症消退介质，并促进银屑病发展。本项目拟在细胞和动物水平上，明确miR-183通过ALOX15对多种促炎症消退介质的调控作用和机制；阐明miR-183对银屑病发病的影响。通过对关键分子miR-183、ALOX15进行干预，抑制银屑病皮损的发展，为治疗银屑病提供新的靶点和理论基础。

Neutrophils chemotaxis, abnormal proliferation of keratinocytes and differentiation imbalances of lymphocyte form the pathological basis of psoriasis, which well correspond to the effect of anti and pro-resolving inflammation of pro-resolving mediators, and it has been confirmed that they can inhibit the formation of psoriasis. We demonstrated that the expression of pro-resolving mediators and ALOX15, the key enzyme in pro-resolving mediator production, were down-regulated in psoriasis skin lesion. It was reported that the expression of miR-183 was obviously increased psoriasis lesions, we also found the high level expression of miR-183 and enhanced cell proliferation in lipopolysaccharide induced activated-keratinocytes. Through gene sequence comparison, we found that it exists the binding site of miR-183 in the 3’-UTR of ALOX15. We propose a hypothetical, miR-183 regulate the expression of pro-resolving mieditors through ALOX15 pathway, and promote the development of psoriasis. This project intends to clarify the effect and molecular mechanism of the regulation of the expression of pro-resolving mieditors through miR-183/ALOX15 pathway, and investigate the role of miR-183 on the formation of psoriasis in cellular and animal level. By the interference with key molecules such as miR-183 and ALOX15, to inhibit the formation of psoriasis, this study could provide new theoretical basis and new target to the therapy of psoriasis.