Abstract
Staphylococcus aureus (S. aureus) infection leads to a severe inflammatory response and causes acute lung injury (ALI), eventually threatening human life. Therefore, it is of importance to find an agent to inhibit inflammation and reduce ALI. Here, we found that costunolide, a sesquiterpene lactone, displays anti-inflammatory effects and ameliorates heat-killed S. aureus (HKSA)-induced pneumonia. Costunolide treatment attenuated HKSA-induced murine ALI in which pulmonary neutrophil infiltration was inhibited, lung edema was decreased, and the production of pro-inflammatory cytokines was significantly reduced. In addition, costunolide dose-dependently inhibited the generation of IL-6, TNF-α, IL-1β, and keratinocyte-derived cytokine (KC), as well as the expression of iNOS, in HKSA-induced macrophages. Furthermore, costunolide attenuated the phosphorylation of p38 MAPK and cAMP response element-binding protein (CREB). Collectively, our findings suggested that costunolide is a promising agent for alleviating bacterial-induced ALI via the inhibition of the MAPK signaling pathways.
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Acknowledgements
This work was supported by the National Key Research and Development Program of China (2017YFC0908500) and National Natural Science Foundation of China (81773741, 81573438, 31741038, and 31770921).
Author contributions
FQ, JW, YC, and YD designed the study and drafted the manuscript. YC, YD, BZ, LG, and KY performed the experiments and data analysis. LS provided suggestions regarding the experimental design, data analysis and discussion.
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Chen, Yt., Du, Y., Zhao, B. et al. Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation. Acta Pharmacol Sin 40, 1040–1048 (2019). https://doi.org/10.1038/s41401-018-0192-6
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DOI: https://doi.org/10.1038/s41401-018-0192-6
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