TY - JOUR
T1 - Redox stress unbalances the inflammatory cytokine network
T2 - Role in autoinflammatory patients and healthy subjects
AU - Lavieri, Rosa
AU - Rubartelli, Anna
AU - Carta, Sonia
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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-1b 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.
AB - 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-1b 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.
KW - ATP secretion
KW - Interleukin-1 family
KW - NLRP3 inflammasome
KW - TLR agonist
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U2 - 10.1189/jlb.3MR0415-159R
DO - 10.1189/jlb.3MR0415-159R
M3 - Article
AN - SCOPUS:84953439482
VL - 99
SP - 79
EP - 86
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 1
ER -