[Caspase-1 inhibitor AC-YVAD-CMK blocks IL-1β secretion of bone marrow-derived macrophages induced by Acinetobacter baumannii]

Abstract

Objective To explore the effect of caspase-1 selective inhibitor AC-YVAD-CMK on IL-1β secretion of bone marrow-derived macrophages (BMDMs) induced by Acinetobacter baumannii (A. baumannii). Methods Macrophages were separated from C57BL/6 mice which were stimulated using different concentrations of A. baumannii. The level of IL-1β in the culture supernatant was detected by ELISA. The expression of pro-IL-1β mRNA and protein were detected using the real-time quantitative PCR and Western blot analysis, respectively. The role of caspase-1 in the secretion of IL-1β was tested by AC-YVAD-CMK treatment to block caspase-1. Pneumonia models in C57BL/6 mice were prepared by A. baumannii inoculation. The level of IL-1β in bronchoalveolar lavage fluid (BALF) and the morphology of lung were detected by ELISA or HE staining, respectively. Results IL-1β level in the culture supernatant was up-reregulated by A. baumannii stimulation in a dose-dependent manner. The expression of pro-IL-1β mRNA and protein were not significantly changed with A. baumannii stimulation. Mature IL-1β secretion was blocked by AC-YVAD-CMK either in vitro or in vivo. The damage of lung induced by A. baumannii infection in mice was ameliorated by AC-YVAD-CMK. Conclusion AC-YVAD-CMK alleviates pulmonary pathological damage by reducing the caspase-1-mediated IL-1β secretion.