Mechanism of sterile inflammation triggered by cell injury

• Main Authors: Wei-Ting Li, 李威霆
• Other Authors: Chun-Jen Chen
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/01140985151543329855

碩士 === 國立臺灣大學 === 微生物與生化學研究所 === 97 === Cell injury is one of the principal stimuli of inflammation, which leads to the pathogenesis of many diseases. Here our research aimed to further delineate the mechanisms behind this type of sterile inflammation. Our experiments were designed to address four aspects including 1) the source of interleukin-1α (IL-1α) generation, 2) the role of mast cells in inflammation, 3) the function of tumor necrosis factor (TNF)-α in sterile inflammation, and 4) the mechanisms of neutrophil activation. We found that IL-1α is potentially a damage-associated molecular pattern (DAMP) released from necrotic cells. In a cell injury-induced peritonitis model, we showed that neutrophil infiltration was markedly reduced in mice depleted of mast cells with compound 48/80. In the acetaminophen (AAP)-induced liver injury model, our data revealed that the level of injury was markedly reduced in TNFR1-deficient mice, and leukocyte infiltration was also affected. We also analyzed whether neutrophils could be stimulated by necrotic cells directly and/or indirectly, and our results showed that necrotic cells could both directly and indirectly activate neutrophils to release O2−, which might be associated with the IL-1α released from necrotic cells. Overall our findings provide new insights on how interleukin-1α (IL-1α), mast cells, and TNF-α, may play their roles in regulating the sterile inflammation induced by cell injury, and how neutrophils are activated once they are recruited to the injured site. Further studies will be carried out to support our models of how these factors link each other in the sterile inflammatory response.