Inhibition of inflammasome activation improves lung acute injury induced by carrageenan in a mouse model of pleurisy

The inflammasome NLRP3 is a molecular pathway activated by a wide range of cellular insults to elicit
innateimmune defenses through the activation of caspase-1 and the maturation of proinflammatory cytokines, such
as IL-1b and IL-18. The expression of NRLP3 is abnormally elevated in numerous human inflammatory diseases,
including pulmonary diseases. An injection of carrageenan (CAR) into the pleural cavity triggered an acute inflammatory
response, leading to tissue damage, inflammatory exudates, leukocyte infiltration, and increased
myeloperoxidase activity. The aimof this study was to assess the effect of the inflammasome blocking agents BAY
11-7082 (30 mg/kg, i.p.) and Brilliant Blue G (BBG) (45.5 mg/kg, i.p.) in a mouse model of CAR-induced pleurisy.
Treatment with BAY 11-7082 or BBG 1 h after CAR injection attenuated pulmonary membrane thickening and
polymorphonuclear leukocyte infiltration, reduced NF-kB translocation in the nucleus, and inhibited the assembly
of the NRLP3/ASC/caspase-1 complex. Treatment with BAY 11-7082 or BBG also down-regulated iNOS, nitrotyrosine,
and poly-ADP-ribosyl polymerase expression and inhibited CAR-induced apoptosis. Our results demonstrate
that treatment with inflammasome-blocking agents can significantly reduce the development of acute
CAR-induced lung injury.—Fusco, R. Gugliandolo, E., Biundo, F., Campolo, M., Di Paola, R., Cuzzocrea, S. Inhibition
of inflammasome activation improves lung acute injury induced by carrageenan in a mouse model of
pleurisy.