De Plaen Laboratory
Our laboratory is studying the developmental aspects of the inflammatory mechanisms contributing to necrotizing enterocolitis (NEC), a devastating disease of the premature infant, causing sudden bowel inflammation and necrosis. We investigate the role of nuclear factor-kB (NF-kB), a central transcription factor in inflammation, in acute bowel injury, using animal models of NEC. Our hypothesis is that necrotizing enterocolitis is due to the prolonged activation of NF-kB in the premature intestine in response to bacterial products and locally produced inflammatory lipid mediators, such as platelet-activating factor (PAF). In the premature infant, bacterial colonization and an initial inflammatory response result in persistent NF-kB activation. This prolonged activation leads to the upregulation of pro-inflammatory cytokines (e.g., TNF), chemokines (e.g. macrophage inflammatory protein-2 (MIP-2)), and of adhesion molecules (e.g., ICAM-1), in an amplification phase of inflammation, resulting in further neutrophil influx and activation, and subsequent irreversible tissue injury and necrosis. We are also examining how the regulation of the inflammatory response develop in the intestine and exploring potential therapeutic agents that would block the progression of NEC, decreasing its morbidity and mortality.
Xueli Liu, MD