Lysophosphatidylcholine activates caspase-1 by bringing about release of ATP and sensitization of purinergic receptor

Abstract

Abstract Lysophosphatidylcholine (LPC) is one of the major damage associated molecular patterns (DAMP) released during inflammation and infection. It generates inflammatory responses from different cell types including macrophages and neuronal cells, and causes demyelination in experimental models of neuroinflammation. LPC activates cellular responses through GPCR dependent and independent signaling. Recently, it has been shown to bring about release of IL-1β through inflammasome-mediated activation of caspase-1. However, the exact mechanism by which LPC stimulates inflammasomes has not been investigated. In this study, we show that LPC triggers release of ATP from cells and activates purinergic signaling, which produces cytotoxicity and caspase-1 – dependent production of IL-1β. LPC activates caspase-1 in a G-αi independent manner. Treatment with apyrase or inhibition of P2X7 receptor reduces LPC - mediated release of LDH and IL-1β. These results identify induction of ATP-release as the critical first trigger by which LPC brings about caspase-1 – dependent inflammatory response.