Methods: In our study the inflammasome was activated by ATP and H2O2 (known nflammasome activators in acute lung injury) in the absence or presence of D series resolvins, resolvin D1 and resolvin D2. Inflammasome activation was assessed by analyzing IL-1β release (end product of inflammasome activation) and caspase-1 cleavage (indicator of inflammasome activation) in THP-1 cells. Further inflammasome was activated in the presence or absence of resolvin in THP-1 cells, and supernatants from these cells were added to A549 cells and human primary small airway epithelial cells (HPSAEC) to study inflammasome mediated functional effects.
Results: Our results indicate that resolvin treatment ameliorates inflammasome activation as indicated by decreased caspase-1 activity and IL-1β release. In addition resolvin treatment inhibits inflammasome mediated epithelial cell activation as indicated by suppressed IL-8 release and decreased and ICAM expression.
Conclusions: These novel findings suggest that resolvins can be used to modulate the inflammasome activity as well as blunt the effects of the IL-1β mediated cytokine storm stemming from inflammasome activation. These results may offer a therapeutic approach to airway diseases such as asthma, where ungoverned pro-inflammatory cytokine secretion exacerbates the disease pathology.