Surfactant inhibits ATP-induced release of interleukin-1β in human monocytes.

Background:

Interleukin-1β (IL-1β) is a pro-inflammatory cytokine involved in host defense. However, IL-1β importantly contributes to acute lung injury. In response to a first danger signal such as lipopolysaccharide, pro-IL-1β is synthesized by mononuclear phagocytes. Extracellular ATP is a prototypical second signal, which results in inflammasome activation, proteolytic cleavage and release of IL-1β. In contrast to IL-1β, pulmonary surfactant has anti-inflammatory properties. Here, we test the hypothesis that surfactant inhibits ATP-induced release of IL-1β from monocytes.

Methods:

Lipopolysaccharide-primed monocytic U937 cells and primary human monocytes were stimulated for 30 min with BzATP in the presence of different concentrations of natural or synthetic surfactant, recombinant surfactant protein-C (rSP-C), phosphatidylserine, and dipalmitoylphosphatidylcholine (DPPC). IL-1β was detected in the supernatants by ELISA.

Results:

Natural and synthetic surfactant dose-dependently inhibited IL-1β release from U937 cells. DPPC was the active constituent of surfactant, whereas rSP-C and phosphatidylserine were inactive. The effect of DPPC was antagonized by nicotinic antagonists mecamylamine, α-bungarotoxin and strychnine, significantly blunted after silencing the expression of nicotinic acetylcholine receptor subunit α9 by siRNA, and was also visible in primary cells.

Conclusions:

The surfactant constituent DPPC efficiently inhibits ATP-induced release of IL-1β from monocytes by a mechanism, which involves nicotinic acetylcholine receptors.

*Presenting author