Hypothetical role of some disregulated BALf proteins in mechanisms driving SSc-related lung fibrosis. Inflammation is thought to be the main mechanism driving lung fibrosis in scleroderma patients. In this complex inflammatory process several pathways are involved, including the activation of T cells and epithelial cells, the secretion of pro-inflammatory cytokines and growth factors, and fibroblast proliferation. Furthermore, products from the coagulation cascade and oxidative stress may contribute to fibrogenesis. The upregulation of calgranulin B (Cal B), cytohesin-2 and calumenin might favor inflammation and fibrogenesis, whereas the downmodulation of the protective factors glutathione S-transferase P (GSTP), Cu–Zn superoxide dismutase (SOD) and cystatin SN may amplify tissue injury and inflammation. MMP, matrix metalloproteinases; TIMP, tissue inhibitor of matrix metalloproteinases; ROS, reactive oxygen species; RNS, reactive nitrogen species; O2-, superoxide; H2O2, hydrogen peroxide; NO, nitric oxide; SScFib+, systemic sclerosis patients with lung fibrosis; SScFib-, systemic sclerosis patients without lung fibrosis.