Figure 8

Developmental Paradigm for Cystic Fibrosis Lung Fibrosis Based on TIUKO CF Rat and Developmental Studies in Mice, Rats, and Non-human Primates. In Panel A CFTR is shown as one member of a developmental cascade required for normal secretory epithelium development. Included in this pathway are other cytokines, possibly MRP8/14. In normal development in the presence of CFTR feedback mechanisms either completely inhibit or at least decrease the expression of these developmentally active cytokines. In the absence of CFTR, Panel B, the secretory epithelium fails to differentiate properly. Failed development leads to an immature epithelium that does not exhibit the feedback function necessary for inhibition of developmentally required cytokines. Expression of these cytokines in the permanent, developmental immature, CF lung leads to activation of inflammatory cells once the immune system matures post-natal. Constitutive, chronic inflammation would explain the lung fibrosis and inflammatory disease seen in CF patients