TLR4 and Barrett esophagus: In BE and EAC, the activation of TLR-4 can directly affect the expression of cyclooxygenase-2 (COX-2), which occurs through NF-κB-independent mechanisms, such as mitogen- and stress-activated kinase (MSK) and mitogen-activated protein kinase (MAPK), that potentially involve altered epigenetic factors [123,131] (Figure 4).