Differential IL-1β secretion by monocyte subsets is regulated by Hsp27 through modulating mRNA stability

Eva Hadadi, Biyan Zhang, Kajus Baidzajevas, Nurhashikin Yusof, Kia Joo Puan, Siew Min Ong, Wei Hseun Yeap, Olaf Rotzschke, Endre Kiss-Toth, Heather L Wilson, Siew Cheng Wong

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

Monocytes play a central role in regulating inflammation in response to infection or injury, and during auto-inflammatory diseases. Human blood contains classical, intermediate and non-classical monocyte subsets that each express characteristic patterns of cell surface CD16 and CD14; each subset also has specific functional properties, but the mechanisms underlying many of their distinctive features are undefined. Of particular interest is how monocyte subsets regulate secretion of the apical pro-inflammatory cytokine IL-1β, which is central to the initiation of immune responses but is also implicated in the pathology of various auto-immune/auto-inflammatory conditions. Here we show that primary human non-classical monocytes, exposed to LPS or LPS + BzATP (3’-O-(4-benzoyl)benzyl-ATP, a P2X7R agonist), produce approx. 80% less IL-1β than intermediate or classical monocytes. Despite their low CD14 expression, LPS-sensing, caspase-1 activation and P2X7R activity were comparable in non-classical monocytes to other subsets: their diminished ability to produce IL-1β instead arose from 50% increased IL-1β mRNA decay rates, mediated by Hsp27. These findings identify the Hsp27 pathway as a novel therapeutic target for the management of conditions featuring dysregulated IL-1β production, and represent an advancement in understanding of both physiological inflammatory responses and the pathogenesis of inflammatory diseases involving monocyte-derived IL-1β.
Original languageEnglish
JournalScientific Reports - Nature
Volume6
DOIs
Publication statusPublished - 2016
Externally publishedYes

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