Figure 5.

Sepsis-Causing Microbial Agents Sensed by Toll-Like Receptors and Other Extracellular and Intracellular Detectors Activate Multiple Transcription Factors in Immune and Non-Immune Cells (e.g., Endothelial and Epithelial Cells). Signals generated by these receptors/sensors/channels activate at least 7 families of stress-responsive transcription factors (SRTFs) and metabolic transcription factors (MTFs) Please note that the AP1 complex comprises two distinct transcription factors, cFos and cJun. Transcription factors are ferried to the inflammatory and/or metabolic regulomes in the nucleus by nuclear transport shuttles (importin α5 and importin β1) that are selectively controlled by the Nuclear Transport Checkpoint Inhibitors (NTCIs) (see text for details). Thus, selective nuclear blockade shields the inflammatory and metabolic regulomes in the nucleus thereby reducing the activation of a myriad (in thousands) of genes responding to sepsis. NPC, Nuclear Pore Complex.