Collagen vascular diseases associated with interstitial lung diseases

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Interstitial lung diseases (ILD) are a diverse group of chronic disorders affecting the distal lung, often unresponsive to current therapies and leading to lung parenchyma distortion and rapid respiratory failure. The disease's pathogenesis remains partially understood, with conditions like idiopathic pulmonary fibrosis (IPF) linked to initial alveolar epithelial cell injury, ER-stress, and apoptosis of type II alveolar epithelial cells (AECII). Collagen vascular diseases (CVD), which are immunologically mediated inflammatory disorders affecting connective tissue and vessels, frequently involve the lungs, particularly in Polymyositis (PM), Dermatomyositis (DM), and Systemic Sclerosis (SSc), where ILD significantly impacts morbidity and mortality. Autoantibodies, such as anti-histidyl-tRNA-Synthetase in PM/DM and various anti-Topoisomerase antibodies in SSc, are predictive of pulmonary involvement. This project hypothesized that these autoantibodies induce ILD development in CVD through AECII injury, leading to ER-stress and apoptosis. To investigate, HisRS, Topo1, Topo2α, and Topo2β were silenced in A549 cells, and topoisomerase inhibition was performed using topotecan and etoposide. Results indicated that silencing did not induce ER-stress or apoptosis, while topoisomerase inhibition did. Immunohistochemistry of lung sections from an SSc patient revealed ER-stress and apoptosis in AECIIs, suggesting that autoantibodies in CVD