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S100A8 and S100A9 Induce Cytokine Expression and Regulate the NLRP3 Inflammasome via ROS-Dependent Activation of NF-[kappa]B.sup.1
Ist Teil von
PloS one, 2013-08, Vol.8 (8), p.e72138
Ort / Verlag
Public Library of Science
Erscheinungsjahr
2013
Link zum Volltext
Quelle
EZB Free E-Journals
Beschreibungen/Notizen
S100A8 and S100A9 are cytoplasmic proteins expressed by phagocytes. High concentrations of these proteins have been correlated with various inflammatory conditions, including autoimmune diseases such as rheumatoid arthritis and Crohn's disease, as well as autoinflammatory diseases. In the present study, we examined the effects of S100A8 and S100A9 on the secretion of cytokines and chemokines from PBMCs. S100A8 and S100A9 induced the secretion of cytokines such as IL-6, IL-8, and IL-1[beta]. This secretion was associated with the activation and translocation of the transcription factor NF-[kappa]B. Inhibition studies using antisense RNA and the pharmacological agent BAY-117082 confirmed the involvement of NF-[kappa]B in IL-6, IL-8, and IL-1[beta] secretion. S100A8- and S100A9-mediated activation of NF-[kappa]B, the NLR family, pyrin domain-containing 3 (NLRP3) protein, and pro-IL-1[beta] expression was dependent on the generation of reactive oxygen species. This effect was synergistically enhanced by ATP, a known inflammasome activator. These results suggest that S100A8 and S100A9 enhance the inflammatory response by inducing cytokine secretion of PBMCs.