Redox stress unbalances the inflammatory cytokine network: role in autoinflammatory patients and healthy subjects

• Published in: Journal of leukocyte biology Vol. 99; no. 1; pp. 79 - 86
• Main Authors: Lavieri, Rosa, Rubartelli, Anna, Carta, Sonia
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.01.2016
• Subjects: Adenosine Triphosphate - metabolism; Animals; ATP secretion; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Cryopyrin-Associated Periodic Syndromes - immunology; Cryopyrin-Associated Periodic Syndromes - metabolism; Cytokines - biosynthesis; Cytokines - metabolism; Healthy Volunteers; Humans; Inflammasomes - immunology; Inflammasomes - metabolism; Inflammation - immunology; Inflammation - metabolism; Inflammation Mediators - metabolism; Interleukin 1 Receptor Antagonist Protein - metabolism; Interleukin-1beta - metabolism; interleukin‐1 family; Monocytes - immunology; Monocytes - metabolism; NLRP3 inflammasome; Oxidation-Reduction; Oxidative Stress; Reviews; Signal Transduction; TLR agonist; interleukin-1 family; NLRP3 inflammasome; ATP secretion; TLR agonist
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.3MR0415-159R

Review on the interplay between stress and cytokine dysregulation in inflammation, in both healthy individuals and CAPS patients. 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.