Figure 9. Model describing expression loop between p53 and the TLR gene family in response to chromosome and inflammation stresses.

DNA metabolic stress is induced by both environmental factors and endogenous sources, such as host-derived reactive oxygen species (ROS) generated downstream of Toll-like Receptors and pro-inflammatory cytokines. DNA damage/stress activates p53-dependent and independent (“X”) pathways that in turn induce expression of TLRs. Increased TLR expression sensitizes the cell to both exogenous, pathogen-associated molecular patterns (PAMPs) and endogenous, damage-associated molecular patterns (DAMPs) released during tissue injury which, in this loop, lead to further ROS.