Abstract
Oxidative stress and endoplasmic reticulum (ER) stress are related states that can occur in cells as part of normal physiology but occur frequently in diseases involving inflammation. In this article, we review recent findings relating to the role of oxidative and ER stress in the pathophysiology of acute and chronic nonmalignant diseases of the lung, including infections, cystic fibrosis, idiopathic pulmonary fibrosis and asthma. We also explore the potential of drugs targeting oxidative and ER stress pathways to alleviate disease.
Highlights
Oxidative stress and endoplasmic reticulum (ER) stress are related states that can occur in cells as part of normal physiology but which have been linked in the pathophysiology of many diseases, diseases involving acute or chronic inflammation.[1]
Cystic fibrosis is a disease where on face value one would predict the development of ER stress because of (1) intrinsic misfolding of the CFTR protein in the case of many mutations, including the common F508del mutation that results in misfolding of all the protein and complete absence of CFTR on the cell surface; (CFTR is normally expressed by a variety of different epithelial cell types but most highly in submucosal gland epithelium); (2) chronic bacterial infection and frequent exacerbations due to viral infection; (3) chronic complex inflammation with activation of both innate immunity and adaptive immunity; and (4) chronic mucus overproduction increasing the ER biosynthetic load of mucin-secreting cells
In sepsis/LPS-induced lung injury, both ER stress and autophagy occur and the systemic factor cold-induced RNA-binding protein (CIRP), local inflammatory cytokines such as IL-17 and neutrophil activation have been linked with the development of ER stress and activation of the unfolded protein response (UPR).[104,105,106]
Summary
TO OXIDATIVE AND ER STRESSOxidative stress and endoplasmic reticulum (ER) stress are related states that can occur in cells as part of normal physiology but which have been linked in the pathophysiology of many diseases, diseases involving acute or chronic inflammation.[1].
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