Function and mechanism of pyrin and IL-10 in the regulation of the inflammasome in pulmonary vascular endothelial cells following hemorrhagic shock.

Abstract

The present study aimed to evaluate the function of pyrin and interleukin-10 (IL-10) and the potential mechanisms underlying the regulation of inflammation in pulmonary vascular endothelial cells (ECs) following hemorrhagic shock (HS). Adult female Sprague-Dawley rats were divided into 4 groups (n=6 in each group) to examine the changes in pyrin expression following HS-lipopolysaccharide (LPS) administration, including the following groups: A sham operation (SM) + tracheal injection of saline (SAL) group; a HS + SAL group; a SM + LPS group (with a tracheal injection of endotoxin); and a HS + LPS group. An additional 4 groups were used to evaluate the function of IL-10, by the additional intratracheal injection of recombinant IL-10. Western blot analysis and immunofluorescence were performed in order to investigate the changes to pyrin and IL-10 expression in pulmonary vascular ECs. The expression levels of pyrin in the SM + LPS group were significantly increased in comparison with the SM + SAL group (P<0.01). Additionally, the expression levels of pyrin were significantly increased in the HS + LPS group compared with the HS + SAL group (P<0.01). The expression levels of caspase-1 were significantly increased in the HS + LPS group compared with those in the other three groups (P<0.01). The expression levels of pyrin in the HS + LPS + IL-10 group were significantly increased compared with the HS + LPS group (P<0.01). The expression levels of caspase-1 were significantly decreased following IL-10 treatment compared with those in the HS + LPS group (P<0.01). Therefore, HS attenuated LPS-induced pyrin expression in pulmonary vascular ECs and may also inhibit the expression of IL-10, resulting in the activation of caspase-1 subsequent to a second LPS insult.