Pyroptosis is a lytic form of cell death that typically involves the release of pro-inflammatory cytokines, such as IL-18 and IL-1β, downstream of caspase-1 activation. As such, pyroptosis is generally regarded as a tissue-damaging process; however, a study from Mehrotra et al. now shows that pyroptotic cells also release mediators — specifically oxylipins and metabolites — that promote tissue repair.

The authors next defined the factors in Pyro−1 supernatants that induce these gene signatures in BMDMs. Using lipidomic analyses, they showed that Pyro−1 supernatants (but not apoptotic cell supernatants from the same type of cell) are enriched in oxylipins, including prostaglandin E2 (PGE2). Moreover, the treatment of target BMDMs with PGE2 induced many of the same genes as the Pyro−1 supernatants. In wound models created on primary mouse fibroblast monolayers, the addition of Pyro−1 supernatants led to increased wound closure compared with the addition of supernatants from live cells or from apoptotic cells. Pyro−1 supernatants also promoted greater migration of fibroblasts and macrophages in transwell migration assays. In addition, supernatants from pyroptotic human monocytes contained PGE2 and promoted wound closure in the fibroblast monolayer systems.