erastin and Inflammation

Cell survival or death is one critical issue in inflammatory responses. Ferroptosis, which is characterized by iron-dependent lethal lipid peroxidation, has been found to participate in the development of cancers, degenerative brain diseases and ischemia-reperfusion injuries. Incorporation of polyunsaturated fatty acids (PUFAs) into cellular membranes represents a vulnerability to invasion of microbials and sterile stimuli. In addition, the competition for iron in the battle between microbials and host cells underlies infection development. Although host cells have been equipped with complex antioxidant systems to combat lethal accumulation of lipid peroxidation, emerging evidence suggests several pathogens may target PUFAs in the cell membrane, and manipulate ferroptosis as a way for pathogen propagation. Moreover, ferroptosis takes part in the progression of sterile inflammations, such as cigarette smoke-induced chronic obstructive pulmonary disease, stroke and ischemia-reperfusion injuries. As iron-dependent oxidative stress and lipid peroxidation are common features for ferroptosis and inflammatory diseases, underlying mechanisms linking such pathological conditions will be discussed in this review. Progress in the research of ferroptosis may shed more light on the etiology and treatment of inflammatory diseases.

Topics: Animals; Atherosclerosis; Ferroptosis; Glutathione; Humans; Infections; Inflammation; Iron; Iron Chelating Agents; Lipid Peroxidation; Lipoxygenases; Membrane Lipids; Oxidative Stress; Piperazines; Reactive Oxygen Species; Reperfusion Injury; Stroke

Damage-associated molecular pattern molecules (DAMPs) are endogenous danger signals that alert the innate immune system and shape the inflammation response to cell death. However, the release and activity of DAMPs in ferroptosis, a recently identified form of regulated necrosis characterized by iron overload and lipid peroxidation, still remain poorly understood. Here, we demonstrate that HMGB1 is a DAMP released by ferroptotic cells in an autophagy-dependent manner. Both type I and II ferroptosis activators, including erastin, sorafenib, RSL3, and FIN56, induce HMGB1 release in cancer and noncancer cells. In contrast, genetic ablation (using ATG5

Topics: Animals; Autophagy; Carbolines; Cell Death; Cell Line, Tumor; Chloroquine; Ferritins; Fibroblasts; HMGB1 Protein; Humans; Immunity, Innate; Inflammation; Iron Overload; Lipid Peroxidation; Macrolides; Mice; Neoplasms; Oximes; Piperazines; Sorafenib; Sulfonamides; Toll-Like Receptor 4