Fig. 1

Mucositis pathobiology: (a) normal tissue; (b) initiation phase and primary injury response. Radio and chemotherapy-induced damages lead to an increase in DNA double strand brakes and ROS production with a consequent induction of cell apoptosis and DAMPS release. DAMPs and ROS signaling promote the NF-κB-mediated transcription of cytokines; (c) amplification of the injury signal. The effectors produced during the previous phase lead to an amplification of the injury signal. The released TNF-α initiates the activation of MAPK that sustains NF-κB activity. During this stage, the primary damage signaling is amplified through positive-feedback loop mechanisms. (d) ulceration. Breaks in the submucosa allows to microorganisms to invade this tissue district leading to mononuclear-infiltrating cells-mediated inflammation response; (e) tissue re-epithelialization. Stimuli from the submucosa extracellular matrix and mesenchyme promote the healing process