Figure 4.

Pathogen detection and ROS-dependent defence and regeneration mechanisms. Epithelial cells are constantly exposed to pathogens. The redox state, the localisation, and the activity of different molecules and proteins are altered in the absence (a) or in the presence (b) of pathogens. Activation of TLRs by PAMPs and Myd88 recruitment induce secretion of ATP, which functions as danger signal and activates NOX. TLR and NOX activation both result in NFκB activation, via Myd88 or src, respectively. NFκB translocates to the nucleus and induces the expression of, for example, chemokines such as IL-8, promoting leukocyte recruitment. Myd88 dimerizes upon H₂O₂ exposure forming disulfide bridges. Src oxidation stabilizes the active conformation of the protease and the oxidation of cysteine residues near the ATP-binding site of the EGFR enhances its activity. Extracellular ATP leads to the activation of the shedding activity of ADAM17. ADAM17 releases soluble TNFα and ligands of the EGFR, such as TGFα and HB-EGF, from the cell surface, whereas TNFα promotes inflammation; signaling via the EGFR leads to regeneration due to induction of cell growth and division (mTNFα: membrane-bound TNFα; mEGFRL: membrane-bound EGFR ligands).