期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 77, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2019.105964
关键词
Protostemonine; MRSA; Acute lung injury; Macrophage; MAPK; NF-kappa B
资金
- National Natural Science Foundation of China, China [81871518, 81901522, 81702799]
- National first-class discipline program of Food Science and Technology [JUFSTR20180101]
- National first-class discipline program of Food Science and Technology, China [JUFSTR20180101]
- Wuxi health and family planning commission, China [Z201810]
- Public Health Research center at Jiangnan University, China [JUPH201805]
- Fundamental Research Funds for the Central Universities, China [JUSRP11955]
Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) caused by gram-positive bacteria threatens human life because effective treatments and medicines is unavailable. Protostemonine (PSN), an active alkaloid mainly isolated from the roots of Stemona sesslifolia, has anti-inflammatory effects on asthma and gram-negative bacteria-induced ALI. Here, we found that PSN exhibits anti-inflammatory effects and alleviates heat-killed methicillin-resistant Staphylococcus aureus (HKMRSA)-induced pneumonia. PSN treatment significantly attenuated HKMRSA-induced pathological injury, pulmonary neutrophil infiltration, tissue permeability and the production of pro-inflammatory cytokines (TNF-alpha, IL-1 beta and IL-6) in murine ALI model. In addition, PSN decreased the content of TNF-alpha, IL-6 and the expression of iNOS, as well as the production of NO in HKMRSA-induced bone marrow derived macrophages (BMDMs). Furthermore, treatment with PSN suppressed the activation of MAPKs (e.g. p38 MAPK, JNK and ERK) and NF-kappa B. Collectively, our results suggest that PSN ameliorates gram-positive bacteria-induced Ail in mice by inhibition of the MAPK and NF-kappa B signaling pathways, and our studies suggest that PSN might be a novel candidate for treating ALI/ARDS.
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