Ironing out the role of ferroptosis in immunity

Immunity, Год журнала: 2024, Номер 57(5), С. 941 - 956

Опубликована: Май 1, 2024

Ferroptosis is a type of regulated cell death that drives the pathophysiology many diseases. Oxidative stress detectable in types death, but only ferroptosis involves lipid peroxidation and iron dependency. originates propagates from several organelles, including mitochondria, endoplasmic reticulum, Golgi, lysosomes. Recent data have revealed immune cells can both induce undergo ferroptosis. A mechanistic understanding how regulates immunity critical to controls responses this dysregulated disease. Translationally, more work needed produce ferroptosis-modulating immunotherapeutics. This review focuses on role immune-related diseases, infection, autoimmune cancer. We discuss immunity, regulation contributes disease pathogenesis, targeting may lead novel therapies.

Язык: Английский

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Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

The FASEB Journal, Год журнала: 2023, Номер 37(6)

Опубликована: Май 18, 2023

Abstract The relationship of obesity and osteoporosis has been widely studied over the past years. However, implications for bone health remain controversial, underlying molecular mechanism is not yet fully understood. This study demonstrated that high‐fat diet‐induced leads to significantly decreased volume/tissue volume (BV/TV), trabecular number (Tb.N), cortical thickness (Ct.Th) male rat femur after mechanical loading effects body weight were controlled. HFD‐induced obese rats exhibited attenuated expression ferroptosis inhibitory protein SLC7A11 GPX4 in tissues, which was correlated with elevated serum TNF‐α concentration. Ferroptosis inhibitor administration could effectively rescue osteogenesis‐associated type H vessels osteoprogenitors, downregulate levels ameliorate loss rats. Since both affect vessel formation, we further investigated interaction between TNF‐α, its impact osteogenesis angiogenesis vitro. In human osteoblast‐like MG63 umbilical vein endothelial cells (HUVEC), TNF‐α/TNFR2 signaling promoted cystine uptake GSH biosynthesis provide protection against low‐dose inducer erastin. While, TNF‐α/TNFR1 facilitated presence high‐dose erastin through ROS accumulation. Moreover, regulated ferroptosis‐induced osteogenic angiogenic dysfunctions based on regulatory role. Meanwhile, inhibitors reduce intracellular overproduction enhance TNF‐α‐treated HUVECs. revealed angiogenesis, provides new insights into pathogenesis regenerative therapy obesity‐related osteoporosis.

Язык: Английский

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Ferroptosis in acute kidney injury following crush syndrome: A novel target for treatment

Journal of Advanced Research, Год журнала: 2023, Номер 54, С. 211 - 222

Опубликована: Янв. 23, 2023

Crush syndrome (CS) is a kind of traumatic and ischemic injury that seriously threatens life after prolonged compression. It characterized by systemic inflammatory reaction, myoglobinuria, hyperkalemia acute kidney (AKI). Especially AKI, it the leading cause death from CS. There are various cell forms in among which ferroptosis typical form death. However, role has not been fully revealed CS-AKI. This review aimed to summarize evidence CS-AKI its related molecular mechanism, discuss therapeutic significance CS-AKI, open up new ideas for treatment One main pathological manifestations renal tubular epithelial dysfunction death, attributed massive deposition myoglobin. Large amounts myoglobin released damaged muscle deposited tubules, impeding normal tubules function directly damaging with oxidative stress elevated iron levels. Lipid peroxidation damage overload distinguishing features ferroptosis. Moreover, high levels pro-inflammatory cytokines damage-associated molecule pattern molecules (HMGB1, double-strand DNA, macrophage extracellular trap) tissue have shown promote how occurs whether can be target remains unclear. In our current work, we systematically reviewed occurrence underlying mechanism

Язык: Английский

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Nrf2-mediated ferroptosis inhibition: a novel approach for managing inflammatory diseases

Inflammopharmacology, Год журнала: 2024, Номер 32(5), С. 2961 - 2986

Опубликована: Авг. 10, 2024

Язык: Английский

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Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases

Cell Death and Disease, Год журнала: 2024, Номер 15(7)

Опубликована: Июль 4, 2024

Abstract Autoimmune diseases commonly affect various systems, but their etiology and pathogenesis remain unclear. Currently, increasing research has highlighted the role of ferroptosis in immune regulation, with cells being a crucial component body’s system. This review provides an overview discusses relationship between ferroptosis, programmed cell death cells, autoimmune diseases. Additionally, it summarizes key targets such as GPX4 TFR, responses. Furthermore, release multiple molecules, including damage-associated molecular patterns (DAMPs), following by is examined, these molecules further influence differentiation function thereby affecting occurrence progression Moreover, secrete factors or metabolites, which also impact target organs tissues involved Iron chelators, chloroquine its derivatives, antioxidants, calreticulin have been demonstrated to be effective animal studies for certain diseases, exerting anti-inflammatory immunomodulatory effects. Finally, brief summary future perspectives on are provided, aiming guide disease treatment strategies.

Язык: Английский

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Molecular and therapeutic landscape of ferroptosis in skin diseases

Chinese Medical Journal, Год журнала: 2024, Номер 137(15), С. 1777 - 1789

Опубликована: Июль 8, 2024

Regulated cell death (RCD) is a critical physiological process essential in maintaining skin homeostasis. Among the various forms of RCD, ferroptosis stands out due to its distinct features iron accumulation, lipid peroxidation, and involvement inhibitory antioxidant systems. In recent years, an expanding body research has solidly linked emergence disorders. Therefore, understanding mechanisms underlying diseases crucial for advancing therapy prevention strategies. This review commences with succinct elucidation that underpin ferroptosis, embarks on thorough exploration ferroptosis's role across spectrum conditions, encompassing melanoma, psoriasis, systemic lupus erythematosus (SLE), vitiligo, dermatological ailments precipitated by ultraviolet (UV) exposure, scrutinizes potential therapeutic benefits pharmacological interventions aimed at modulating amelioration diseases.

Язык: Английский

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NAT10, an RNA Cytidine Acetyltransferase, Regulates Ferroptosis in Cancer Cells

Antioxidants, Год журнала: 2023, Номер 12(5), С. 1116 - 1116

Опубликована: Май 18, 2023

Recently, we reported that N-acetyltransferase 10 (NAT10) regulates fatty acid metabolism through ac4C-dependent RNA modification of key genes in cancer cells. During this work, noticed ferroptosis as one the most negatively enriched pathways among other NAT10-depleted In current explore possibility whether NAT10 acts an epitranscriptomic regulator pathway Global ac4C levels and expression with ferroptosis-related were assessed via dotblot RT-qPCR, respectively. Flow cytometry biochemical analysis used to assess oxidative stress features. The ac4C-mediated mRNA stability was conducted using RIP-PCR assay. Metabolites profiled LC-MS/MS. Our results showed significant downregulation essential related ferroptosis, namely SLC7A11, GCLC, MAP1LC3A, SLC39A8 Further, a reduction cystine uptake reduced GSH levels, along elevated ROS, lipid peroxidation Consistently, overproduction oxPLs, well increased mitochondrial depolarization decreased activities antioxidant enzymes, support notion induction Mechanistically, level shortens half-life GCLC SLC7A11 mRNA, resulting low intracellular GSH, failing detoxify leading cellular which facilitate induction. Collectively, our findings suggest restrains by stabilizing transcripts order avoid induces oxidation phospholipids initiate ferroptosis.

Язык: Английский

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Combined Toxicity Assessment of Deoxynivalenol and Pb²⁺ on HK-2 Cells Involved in Excessive ROS-Induced Ferroptosis

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 16, 2025

The cocontamination of food by several mycotoxins and heavy metals poses significant health risks, their combined toxic effects remain poorly understood. Particularly, specific studies exploring impact on ferroptosis limited. In this work, we investigated the a mycotoxin, called deoxynivalenol (DON), metal, plumbum (Pb), explored potential mechanisms DON Pb co-occurrence via excessive ROS-induced in HK-2 cells. It was found that toxicity Pb2+ showed synergism at low concentrations an antagonism high concentrations. increase ROS level iron content as well change expression four marker proteins were observed individual groups. Furthermore, addition inhibitor Fer-1 could mitigate imbalance oxidative stress ferroptosis. Our results suggest might pose slight threat to nephrotoxicity due interactions related ferroptosis, which would provide valuable insights into impacts human animal health.

Язык: Английский

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Anti-Inflammatory Effects of Curcumin-Based Nanoparticles Containing α-Linolenic Acid in a Model of Psoriasis In Vitro

Nutrients, Год журнала: 2025, Номер 17(4), С. 692 - 692

Опубликована: Фев. 14, 2025

Background/Objectives. Psoriasis is a common chronic skin inflammatory disorder pathogenetically associated with genetic, environmental, and immunological factors. The hallmarks of psoriatic lesions include sustained inflammation related to alterations in the innate adaptive immune response, uncontrolled keratinocyte proliferation, differentiation, death, as well dysregulated crosstalk between cells keratinocytes. In search novel therapeutic strategies based on use natural products dietary components combine available conventional innovative therapeutics, we explored anti-inflammatory, antioxidant, immunomodulatory activities Curcumin (CU)-based solid lipid nanoparticles (SLNs) carrying omega-3 fatty acid linolenic (LNA) an vitro model psoriasis that had been previously constructed characterized by us. Methods. This consists differentiated THP-1 macrophages (Mφs) NCTC-2544 keratinocytes exposed or not conditioned medium (CM) from Mφs treated Toll-like receptor-7 ligand imiquimod (IMQ). Results. Mφs, treatment CU-LNA-SLNs inhibited IMQ-induced expression proinflammatory cytokines (IL-23, IL-8, IL-6: 43%, 26.5% 73.7% inhibition, respectively, vs IMQ-treated Mφs), hyperproliferative response (12.8% inhibition Mφs) increase cell death observed Mφ-derived CM (64.7% inhibition). Moreover, same conditions, reverted control levels increased two markers ferroptosis, form recently involved pathogenesis (TFRC MDA: 13.4% 56.1% respectively). Conclusions. These results suggest could inhibit inflammation, hyperproliferation lesions, be considered new possible strategy for further evaluated topic vivo.

Язык: Английский

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MAPK14 as a key gene for regulating inflammatory response and macrophage M1 polarization induced by ferroptotic keratinocyte in psoriasis

Inflammation, Год журнала: 2024, Номер 47(5), С. 1564 - 1584

Опубликована: Март 5, 2024

Язык: Английский

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