[Frontiers in Bioscience 7, d1743-1761, August 1, 2002] 1743 MOLECULAR MECHANISMS OF PULMONARY FIBROSIS

1. Abstract 2. Introduction 3. Lessons from the inflammatory pathway 3.1. The paradigm of type 1 or type 2 cytokine network commitment 3.2. Chemokines 3.2.1. Chemokines in inflammatory/fibrotic lung disorders 3.2.2. Chemokines and Th1/Th2 cytokines circuit 3.2.3. Chemokines and angiogenesis 4. The epithelial pathway. Tying loose ends 4.1. Idiopathic pulmonary fibrosis and the alveolar epithelium 4.2. Epithelial cell apoptosis and alveolar re-epithelialization. 4.3. Epithelial cells: The source of profibrotic cytokines/growth factors in IPF 4.4. Alveolar epithelial cells and intra-alveolar coagulation 4.5. Are epithelial cells directly participating in fibrilar collagens accumulation? 5. Fibroblasts/myofibroblasts: the common route for the inflammatory and epithelial pathways to pulmonary fibrosis 5.1. Fibroblast heterogeneity 5.2. First call: Fibroblast migration to the site of lesion 5.3. Second call: Fibroblast proliferation in the site of lesion 5.4. Third and last call: Fibroblasts differentiate into myofibroblasts 5.5. Myofibroblast persistence in the active fibrotic site 5.6. Myofibroblasts and lung fibrogenesis 6. Matrix remodeling: a crucial role for matrix metalloproteinase family 6.1. MMPs/TIMPs relationships in pulmonary fibrosis 7. Genetic susceptibility and pulmonary fibrosis 7.1. Genetic polymorphisms and pulmonary fibrosis 7.2. Gene-gene and gene-gene-environment interactions 7.3. Functional genomics and gene-expression profile 8. Perspective 9. References