Molecular Mechanism of Neutrophil Necroptosis and Its Roles in RA Pathogenesis

Necrosis has recently been demonstrated to be programmatic and energy comsuming, a process termed necroptosis.

In this project, the investigators aim to investigate the mechanisms and the effects ofneutrophil necroptosis and apoptosis: 1. to investigate the cells and the molecular mechanisms that induce neutrophil necroptosis or delay apoptosis, mainly focusing on the roles of HMGB-1,TNF-α and LPS, 2. to illustrate the effects of some molecules such as TLR, TNFR, RIP1/RIP3, Caspase8, ATP and ROS in the process of sigal transduction and membrane damage during necroptosis or apoptosis , 3. to identify the similarities and differences between traditional necrosis and necroptosis in the aspects of morphologigical changes and inflammatory cytokine release, 4. to find out the effects and mechanisms of neutrophil necroptosis or apoptosis in a rheumatoid arthritis mouse model and the therapeutic effect of blocking one or several pathways in the pathogenesis of rheumatoid arthritis.

This study will not only unravel the mechanisms of neutrophil necroptosis and apoptosis, elucidate its roles and significances in inflammation and infection, but also shed new light on anti-inflammatory and anti-infection therapy.