Fig. 10

Schematic diagram of the development of UIP/IPF. In familial and sporadic IPF an underlying gene defect induces apoptosis of pneumocytes, but in addition, some cells undergo senescence (in Fig. 7 these cells highlighted by p16 and p21 stains). Senescent cells release cytokines and growth factors, which induce proliferation of myofibroblasts. Later on, these cells undergo differentiation, become fibroblasts and turn immature collagen-III into mature collagen-I. There are still open questions, such as how much EMT and MET contributes to the continuation of the myofibroblast proliferation, what is the role of bone marrow derived stem cells? In chronic autoimmune and allergic diseases the causing factors are autoimmune mechanisms, deregulation of the immune system, by which probably cytotoxic lymphocytes induce apoptosis and necrosis of pneumocytes, followed by the same downstream inflammatory mechanisms, leading to fibrosis. Mutations of telomerase genes contribute to the senescence process, mutations in surfactant apoprotein genes and MUC5B might be involved in prolongation of the inflammatory status. Heat shock proteins seem to be involved in maintaining the myofibroblast proliferation