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Prolonged Exposure to Lipopolysaccharide Induces NLRP3-Independent Maturation and Secretion of Interleukin (IL)-1beta in Macrophages

 Sujeong Hong  ;  Je-Wook Yu 
 Journal of Microbiology and Biotechnology, Vol.28(1) : 115-121, 2018 
Journal Title
 Journal of Microbiology and Biotechnology 
Issue Date
NLRP3 ; inflammasome ; interleukin-1beta ; lipopolysaccharide
Upon sensing of microbial infections or endogenous danger signals in macrophages, inflammasome signaling plays a significant role in triggering inflammatory responses via producing interleukin (IL)-1beta. Recent studies revealed that active caspase-1, a product of the inflammasome complex, causes maturation of inactive pro-IL-1beta into the active form. However, the underlying mechanism by which this leaderless cytokine is secreted into the extracellular space remains to be elucidated. In this study, we demonstrated that prolonged lipopolysaccharide (LPS) treatment to macrophages could trigger the unexpected maturation and extracellular release of IL-1beta through a nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3)-independent manner. Short-term treatment (less than 6 h) of LPS induced robust production of the IL-1beta precursor form inside cells but did not promote the maturation and secretion of IL-1beta in bone marrow-derived macrophages or peritoneal macrophages. Instead, prolonged LPS treatment (more than 12 h) led to a significant release of matured IL-1beta with no robust indication of caspase-1 activation. Intriguingly, this LPS-triggered secretion of IL-1beta was also observed in NLRP3-deficient macrophages. In addition, this unexpected IL-1beta release was only partially impaired by a caspase-1 and NLRP3 inflammasome inhibitor. Collectively, our results propose that prolonged exposure to LPS is able to drive the maturation and secretion of IL-1beta in an NLRP3 inflammasome-independent manner.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
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