Figure 14.

Graphical representation of the proposed inhibitory mechanism mediated by SLPI. LPS stimulates Toll-like receptor 4 (TLR4) at monocytic cells and induces the synthesis of pro-IL-1β. Extracellular ATP activates the P2X₇R and leads to inflammasome assembly, caspase-1 activation and proteolytic cleavage of pro-IL-1β, and release of mature IL-1β. SLPI released for example from monocytes, activates iPLA2β in an annexin 2 (Anx2)-dependent manner and induces the production and release of an inhibitory low molecular mass factor (LMMF) that functions as an agonist of nicotinic acetylcholine receptors (nAChR). The LLMF in turn activates nACHRs containing subunits α7, α9, and α10, resulting in Src kinase activation, inhibition of P2X₇R function, prevention of pro-IL-1β maturation, and IL-1β secretion.