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Serum Amyloid A Induces NLRP-3-Mediated IL-1β Secretion in Neutrophils

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Title: Serum Amyloid A Induces NLRP-3-Mediated IL-1β Secretion in Neutrophils
Authors: Migita, Kiyoshi / Izumi, Yasumori / Jiuchi, Yuka / Kozuru, Hideko / Kawahara, Chieko / Nakamura, Minoru / Nakamura, Tadashi / Agematsu, Kazunaga / Masumoto, Junya / Yasunami, Michio / Kawakami, Atsushi / Eguchi, Katsumi
Issue Date: 20-May-2014
Publisher: Public Library of Science
Citation: PLoS ONE, 9(5), e96703; 2014
Abstract: Background/Aims: Serum amyloid A (SAA) is an acute phase reactant with significant immunological activities, including effects on cytokine synthesis and neutrophil chemotaxis. Neutrophils can also release cytokines with proinflammatory properties. IL-1β is a key proinflammatory cytokine, the secretion of which is controlled by inflammasome. We investigated the proinflammatory effects of SAA in vitro in relation to the NLRP3 inflammasome in neutrophils. Methodology/Principal Findings: Human neutrophils isolated form healthy subjects were stimulated with serum amyloid A (SAA). The cellular supernatants were analyzed by western blot using anti-IL-1β or anti-caspase-1 antibodies. IL-1β or Nod-like receptor family, pyrin domain containing 3 (NLRP3) mRNA expressions were analyzed by real-time PCR or reverse transcription-PCR (RT-PCR) method. SAA stimulation induced pro-IL-1β mRNA expression in neutrophils. Furthermore, SAA engaged the caspase-1-activating inflammasome, resulting in the production of active IL-1β. SAA-induced pro-IL-1β expression was marginally suppressed by the Syk specific inhibitor, R406, and SAA-induced pro-IL-1β processing in neutrophils was prevented by R406. Furthermore, SAA-induced NLRP3 mRNA expression was completely blocked by R406. Analysis of intracellular signaling revealed that SAA stimulation activated the tyrosine kinase Syk and mitogen-activated protein kinase (MAPK). Conclusions/Significance: These results demonstrate that the innate neutrophil immune response against SAA involves a two-step activation process: an initial signal promoting expression of pro-IL-1β and a second signal involving Syk-dependent activation of the NLRP3 inflammasome and caspase-1, allowing processing of pro-IL-1β and secretion of mature IL-1β.
URI: http://hdl.handle.net/10069/34515
DOI: 10.1371/journal.pone.0096703
Rights: © 2014 Migita et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/34515

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