MAPK8 and chronic rhinosinusitis: Low pH leads to increased junctional permeability through the disruption of protein bridge formation with cell-to-cell adhesion molecules, such as E-cadherin.24 Moreover, even under neutral pH, pepsin can increase the expression of the heat shock protein HSP70 in human nasal epithelial cells by activating the JNK/MAPK signaling pathway.25 This appears to be 1 mechanism through which EER can contribute to ITH and chronic rhinosinusitis.26