Induction of TNFα and IL-6 in response to TLR occurs via activation of gene transcription (Hoshino et al., 1999; Tamandl et al., 2003). The formation of IL-1β also requires TLR4 induction of gene transcription, but requires an additional step, the processing of pro-IL-1β to the mature, active form of IL-1β, which is then released (Bryant and Fitzgerald, 2009) (Fig 1). The processing and release of pro-IL-1β occurs via NLRP3, part of a multiprotein complex referred to as the “inflammasome” (Martinon et al., 2002). A key activator of inflammasome is the ATP purinergic type 2X7 (P2X7) receptor (Ferrari et al., 1997a; Ferrari et al., 2006), although there are examples of NLRP3 independent induction of IL-1β (Bryant and Fitzgerald, 2009; Chae et al., 2011).
