Impacts of magnolol on LPS induced pyroptosis of alveolar epithelial cells by regulating cAMP/PKA/CREB signaling pathway
10.3969/j.issn.1000-484X.2025.10.026
- VernacularTitle:厚朴酚调节cAMP/PKA/CREB信号通路对LPS诱导的肺泡上皮细胞焦亡的影响
- Author:
Rui WANG
1
;
Tiantian XIONG
1
;
Ming LI
1
Author Information
1. 国药葛洲坝中心医院儿科,宜昌 443002
- Publication Type:Journal Article
- Keywords:
Magnolol;
cAMP/PKA/CREB signaling pathway;
LPS;
Alveolar epithelial cells;
Pyroptosis
- From:
Chinese Journal of Immunology
2025;41(10):2463-2468
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate impacts of magnolol(MAG)on lipopolysaccharide(LPS)induced pyroptosis of alveolar epithelial cells by regulating cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP-response element binding protein(CREB)signaling pathway.Methods:Human pulmonary alveolar epithelial cells HPAEC were routinely cultured and randomly divided into Control group(blank medium treatment),LPS induction group(Model group,10 μg/ml LPS),low concentration MAG group(MAG-L group,20 μmol/L MAG),high concentration MAG group(MAG-H group,40 μmol/L MAG)and high concentration MAG+PKA inhibitor H-89 group(MAG-H+H-89 group,40 μmol/L MAG+20 μmol/L H-89).MTT method was applied to detect cell activity.Lactate dehydrogenase(LDH)experiment was applied to detect cytotoxic damage.Scanning electron microscopy was used to observe pyroptosis.Flow cytometry was applied to detect rate of pyroptosis.ELISA was applied to detect levels of cAMP,IL-1β and IL-18 in cell supernatant.Western blot was applied to detect expressions of cell cAMP/PKA/CREB signaling pathway related proteins and pyroptosis related proteins,such as GSDMD,NLRP3,ASC and Caspase-1.Results:Compared with Control group,A490 value of HPAEC cells(48 hours,72 hours),level of cAMP in supernatant,phosphorylation levels of PKA and CREB in Model group were obviously reduced(P<0.05),levels of LDH,IL-1β,IL-18,pyroptosis rate,and expressions of pyroptosis related proteins GSDMD,NLRP3,ASC,Caspase-1 in supernatant were obviously increased(P<0.05),scanning electron microscopy revealed cell swelling with irregular boundaries.Compared with Model group,changes in corresponding indicators of cells in MAG-H group were opposite to the above(P<0.05),and swelling of cells was reduced.H-89 weakened the alleviating effect of MAG on LPS induced pyroptosis of alveolar epithelium.Conclusion:MAG may alleviate LPS-induced alveolar epithelium pyroptosis by activating cAMP/PKA/CREB signaling pathway.