促炎细胞因子
S100A9型
受体
细胞生物学
炎症
S100A8型
潮湿
癌症研究
小分子
生物
癌症
免疫学
癌细胞
化学
生物化学
物理
遗传学
气象学
作者
Tomas Leanderson,David Liberg,Fredrik Ivars
出处
期刊:Endocrine, metabolic & immune disorders
[Bentham Science]
日期:2015-05-22
卷期号:15 (2): 97-104
被引量:22
标识
DOI:10.2174/1871530315666150316123854
摘要
Upon tissue injury and infection both stressed and dying cells can release proteins that normally reside inside the cells. Some of the released proteins become ligands of various cell surface receptors expressed by local cells and such proteins are denoted as damage associated molecular patterns (DAMPs). Binding of some DAMPs to certain cell surface receptors induces signals emanating in the production of pro-inflammatory cytokines, ultimately leading to an inflammatory response. Our laboratory is interested in the S100A9 protein, a bona fide DAMP protein. This protein normally resides inside monocytes and neutrophils and in these cells it forms heterodimers with the S100A8 protein. The S100A8/A9 heterodimer is released in large amounts during several types of inflammatory disease and is currently used clinically as a biomarker in some diseases. The fact that several different proinflammatory functions have been ascribed to this protein makes it a potential target for the development of small molecule inhibitors. We have developed several such inhibitors, some of which are already in phase III clinical development. This review describes our efforts to investigate the biological functions of the S100A9 protein as well as our ongoing efforts of developing second-generation, more specific, small molecule inhibitors of its pro-inflammatory functions. Keywords: Cancer, DAMP, inflammation, inhibitors, receptor, S100 proteins.
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