Gasdermin D-independent IL-1ß secretion by living human monocytic cells
(2018)
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- Abstract
- Interleukin-1β (IL-1β), a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which the mechanism of secretion remains to be established. In murine macrophages, IL-1ß is known to be released through pyroptosis, a highly inflammatory cell death, mediated by gasdermin D (GSDMD) pores at the plasma membrane. Whether gasdermin D is dispensable for IL-1ß secretion in human cells was still unknown. Here we show that human blood monocytes stimulated with LPS alone secrete mature IL-1ß without cell death and without gasdermin D cleavage, while they undergo pyroptosis with gasdermin D cleavage when stimulated with LPS and an activator of the NLRP3 inflammasome. In addition, we show that LPS- stimulated human monocytic THP-1 cells secrete IL-1ß, even after invalidation of the gasdermin D- encoding gene, pointing out to the existence of a pathway of IL-1ß secretion that is cell death- and gasdermin D-independent.
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Six, C. (2018). Gasdermin D-independent IL-1ß secretion by living human monocytic cells. https://hdl.handle.net/2078.5/59351