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Inflammation and DNA damage: cause, effect or both

Pezone, Antonio ; Olivieri, Fabiola ; Napoli, Maria Vittoria ; Procopio, Antonio ; Avvedimento, Enrico Vittorio ; Gabrielli, Armando

Nature reviews. Rheumatology, 2023-04, Vol.19 (4), p.200-211 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Inflammation and DNA damage: cause, effect or both
Autor: Pezone, Antonio ; Olivieri, Fabiola ; Napoli, Maria Vittoria ; Procopio, Antonio ; Avvedimento, Enrico Vittorio ; Gabrielli, Armando
Assuntos: Blood vessels ; Cell cycle ; Cellular Senescence - genetics ; Cytokines ; Deoxyribonucleic acid ; DNA ; DNA biosynthesis ; DNA Damage ; Gene expression ; Humans ; Immune system ; Inflammation ; Kinases ; Mitochondria ; p53 Protein ; Phenotypes ; Senescence ; Signal Transduction ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Protein p53 - pharmacology
É parte de: Nature reviews. Rheumatology, 2023-04, Vol.19 (4), p.200-211
Notas: ObjectType-Article-2
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Descrição: Inflammation is a biological response involving immune cells, blood vessels and mediators induced by endogenous and exogenous stimuli, such as pathogens, damaged cells or chemicals. Unresolved (chronic) inflammation is characterized by the secretion of cytokines that maintain inflammation and redox stress. Mitochondrial or nuclear redox imbalance induces DNA damage, which triggers the DNA damage response (DDR) that is orchestrated by ATM and ATR kinases, which modify gene expression and metabolism and, eventually, establish the senescent phenotype. DDR-mediated senescence is induced by the signalling proteins p53, p16 and p21, which arrest the cell cycle in G1 or G2 and promote cytokine secretion, producing the senescence-associated secretory phenotype. Senescence and inflammation phenotypes are intimately associated, but highly heterogeneous because they vary according to the cell type that is involved. The vicious cycle of inflammation, DNA damage and DDR-mediated senescence, along with the constitutive activation of the immune system, is the core of an evolutionarily conserved circuitry, which arrests the cell cycle to reduce the accumulation of mutations generated by DNA replication during redox stress caused by infection or inflammation. Evidence suggests that specific organ dysfunctions in apparently unrelated diseases of autoimmune, rheumatic, degenerative and vascular origins are caused by inflammation resulting from DNA damage-induced senescence.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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Inflammation and DNA damage: cause, effect or both

Pezone, Antonio ; Olivieri, Fabiola ; Napoli, Maria Vittoria ; Procopio, Antonio ; Avvedimento, Enrico Vittorio ; Gabrielli, Armando

United States: Nature Publishing Group

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