[Introduction] Sepsis is a pathophysiological condition in which organ injuries progress due to infection. In 1992, sepsis was internationally defined as systemic inflammatory response syndrome (SIRS) associated with infection. Cytokine storm is the pathophysiological background of the syndrome SIRS. Since 2016, the international definition has been changed to Sepsis-3 to modify the concept of sepsis, in which organ dysfunctions progress due to infection. Infectious diseases exacerbate organ damages as a second attack to many famous diseases such as cancer, stroke, acute myocardial infarction and diabetes. In this symposium, we will discuss the pathophysiological features of sepsis and the roles of the transcription factors involved.
[Contents] The presentation will proceed from the following four contents. 1. Differences of the situation and condition at which sepsis begins: Sepsis pathology is affected by the underlying conditions such as the normal, the already occurring inflammation, and the influence of proliferative cytokines. In addition, the septic response is reduced in aging and impaired protein synthesis. 2. Receptor activity: "Alert cells" death due to activation of Toll-like receptors and Death receptors involved in sepsis is discussed. "Alert cells" are defined as cells that recognize inflammatory molecules and produce inflammatory agents while accelerating own cell death. 3. Transcription factor regulation: Discuss the role of transcription factors such as nuclear factor-kB (NF-kB), activator protein-1 (AP-1), and signal transducer and activator of transcription 3 (STAT-3) that are activated in sepsis. 4. Transcription factor network that forms sepsis pathology: An activity change between transcription factors will be discussed.
[Conclusions] Various transcription factors are activated and promote catabolism of proteins and lipids in sepsis and septic shock. We discuss the possibility of novel drug discovery in sepsis and septic shock.