Janus kinase/signal transducer and activator of transcription pathway and sepsis after trauma / 解放军医学杂志

ABSTRACT

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) are a major signal transduction pathway in controlling and regulating a number of cytokine-mediated responses, including interferon-?, interleukin-1 (IL-1), IL-6, IL-10 and IL-4. The JAK/STAT pathway is particularly elegant because of its very rapid and simple cytoplasm-to-nucleus signaling. Recently, it has been found that JAK/STAT pathway might also be involved in the regulation of high mobility group box-1 protein (HMGB1), which plays an important role as a potential late mediator of sepsis. Inhibition of the activation of JAK/STAT pathway can down-regulate the gene expression of HMGB1 in vital organs, especially in the liver and lungs. In addition, treatment with JAK/STAT pathway inhibitors can effectively prevent the occurrence and development of multiple organ dysfunction syndrome following sepsis, and the probable underlying mechanism of which involves a reduction of direct or indirect harmful effect of HMGB1. Over the past few years, numerous investigations have contributed to our knowledge of the JAK/STAT pathway and its role in cytokine-mediated abnormality of immune function as well as inflammatory response during sepsis, and it might be helpful in further identifying a potential strategy of intervention for posttraumatic or postburn sepsis. This review summarizes the salient features of JAK/STAT pathway and focuses on the pathophysiological role of JAK/STAT in regulating proinflammatory cytokine activity and HMGB1 expression in vivo.