title: Redox stress unbalances the inflammatory cytokine network: role in autoinflammatory patients and healthy subjects.
abstract: The cell stress and redox responses are increasingly acknowledged as factors contributing to the generation and development of the inflammatory response. Several inflammation-inducing stressors have been identified, inside and outside of the cell. Furthermore, many hereditary diseases associate with inflammation and oxidative stress, suggesting a role for mutated proteins as stressors. The nucleotide-binding oligomerization domain, leucine-rich repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome is an important node at the crossroad between redox response and inflammation. Remarkably, monocytes from patients with mutations in the NLRP3 gene undergo oxidative stress after stimulation with minute amounts of TLR agonists, resulting in unbalanced production of IL-1β and regulatory cytokines. Similar alterations in cytokine production are found in healthy monocytes upon TLR overstimulation. This mini-review summarizes recent progress in this field, discusses the molecular mechanisms underlying the loss of control of the cytokine network following oxidative stress, and proposes new therapeutic opportunities.
authors.affiliation: Cell Biology Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Lavieri
authors.affiliation: Cell Biology Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Rubartelli
authors.affiliation: Cell Biology Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliera Universitaria San Martino-Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy sonia.carta@hsanmartino.it.
authors.forename: Sonia
authors.initials: S
authors.lastname: Carta
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D056587:Cryopyrin-Associated Periodic Syndromes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D000255:Adenosine Triphosphate
keywords: ATP secretion; NLRP3 inflammasome; TLR agonist; interleukin-1 family