Pellino1 promoted inflammation in lung injury model of sepsis by TRAF6/ NF-κB signal pathway

BACKGROUND: This study was designed to investigate the role of Pellino1 in lung injury model of sepsis and its anti-inflammation mechanism. METHOD: C57BL/6 male mice (6–7 weeks old) and Pellino1(−/−) male mice were subjected to laparotomy followed by extracorporeal cecum mobilization and ligation. THP-1 cells were treated with 500 ng/ml of LPS for 4 h. Both mRNA and protein expression of Pellino1 was increased at time dependence in lung tissue of lung injury model of sepsis mice. Knockout of Pellino1 attenuated lung injury and inhibited inflammation of sepsis mice. While Pellino1 protein enhanced lung injury and increased inflammation of sepsis mice. Pellino1 promoted inflammation in in vitro model of lung injury by TRAF6/ NF-κB signal pathway. RESULT: TRAF6 inhibitor attenuated the effects of Pellino1 on inflammation and lung injury in mice of sepsis. Similarly, NF-κB inhibitor also suppressed the effects of Pellino1 on inflammation and lung injury in mice of sepsis. The activation of TRAF6 or induction of NF-κB attenuated the effects of Pellino1 on inflammation in in vitro model of sepsis. The inhibition of TRAF6 or suppression of NF-κB reduced the effects of Pellino1 on inflammation in in vitro model of sepsis. CONCLUSIONS: These results suggested that Pellino1 promoted inflammation in lung injury model of sepsis by TRAF6/ NF-κB signal pathway.