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To explore the effect of double-stranded RNA-dependent kinase (PKR) in acute lung injury (ALI) and resultant acute respiratory distress syndrome (ARDS). A mouse model of lipopolysaccharide (LPS)-induced ALI was used to evaluate the levels of phosphorylated (p)-PKR and NLRP3 in lung tissue, and the protective effects of a PKR inhibitor on lung injury. And in vitro, macrophages were incubated with LPS, with or without PKR inhibitor pre-treatment. It was observed that the levels of p-PKR protein and NLRP3 protein were significantly increased compared with those in control tissues after LPS administration. Meanwhile, treatment with PKR inhibitor decreased inflammation, injury score, wet/dry weight ratio, bronchoalveolar lavage fluid (BALF) protein levels, neutrophil count in BALF, myeloperoxidase activity and expression of high-mobility group box1(HMGB1) and interleukin(IL)-1β in the lungs of LPS-challenged mice. In vitro, we demonstrated that the levels of p-PKR and NLRP3, and cell mortality rate were increased in macrophages which were incubated with LPS compared with those without LPS administration, and PKR inhibitor significantly suppressed the level of NLRP3, caspase-1, HMGB1 and IL-1β. These results indicate that PKR plays a key role in ALI through NLRP3-pyrotosis pathway and pharmacological inhibition of PKR may have potential therapeutic effects in the treatment of patients with ALI and ARDS. • The role of PKR in the pathogenesis of ALI/ARDS was explored. • Inhibition of PKR protects against LPS-induced ALI by suppressing NLRP3-pyrotosis pathway. • Pharmacological inhibition of PKR may have potential therapeutic effects in the treatment of patients with ALI and ARDS. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a Gram-negative coccobacillus found primarily in hospital settings that has recently emerged as a source of hospital-acquired infections, including bacterial pneumonia. The hLF(1-11) peptide comprising the first 11 N-terminal residues of human lactoferrin exerts antimicrobial activity in vivo and was highly effective against multidrug-resistant A. baumannii strains in vitro and in vivo. Pyroptosis is a caspase-1-dependent inflammatory cell death process and is induced by various microbial infections. In the present study, we investigated the molecular mechanisms that regulate pyroptosis induced by A. baumannii in macrophages. Our results revealed that A. baumannii induced pyroptosis through caspase-1 activation and IL-1β production. We also found that caspase-1 activation and IL-1β maturation in A. baumannii -triggered pyroptotic cell death were reduced by hLF(1-11) treatment. Moreover, hLF(1-11) inhibited the A. baumannii -induced caspase-1 activation and pyroptosis of pulmonary alveolar macrophages in vivo. [ABSTRACT FROM AUTHOR]