Calcium binding protein S100A4 inhibitor Niclosamide regulates inflammatory response of bronchial epithelial cells
10.3969/j.issn.1000-484X.2024.11.004
- VernacularTitle:钙结合蛋白S100A4抑制剂Niclosamide调节支气管上皮细胞炎症反应
- Author:
Ke CHEN
1
;
Shihui MO
;
Shirong YAN
;
Jing LI
;
Tongqian WU
;
Fang YU
Author Information
1. 贵州医科大学医学检验学院,贵阳 550004
- Keywords:
Bronchial epithelial cell;
LPS;
S100A4;
Niclosamide;
ROS;
Tight junction;
Inflammation
- From:
Chinese Journal of Immunology
2024;40(11):2262-2266,2272
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate potential mechanisms of Niclosamide,a calcium-binding protein S100A4 inhibitor,in regulating inflammatory response of bronchial epithelial cells.Methods:Human bronchial epithelial cells BEAS-2B were cultured in vitro and stimulated by LPS or Niclosamide-pretreatment.Inflammatory cytokines and potential signaling molecules expressions were determined by RT-qPCR and Western blot.Intracellular ROS level was quantified by fluorescent probe.Results:Increased ROS level was observed in LPS-stimulated and Niclosamide-pretreatment cells(P<0.05).Compared with control group,mRNA and protein expressions of S100A4 were increased(P<0.05),TLR4/STAT3,MAPK1/3/SIRT1,NF-κB/IKKβ/p65 mRNA expressions were increased(P<0.05),inflammatory cytokines IL-1β and IL-6,tight junction Occludin and ZO-1 mRNA expressions were increased after LPS-treatment(P<0.05),whereas these genetic expressions were downregulated by Niclosamide-pretreatment(P<0.05),except for TLR4/MAPK1 and NF-κB/IKKβ/p65(P>0.05).Western blot showed that compared with control group,LPS-stimulation promoted protein expressions of S100A4,STAT3,MAPK3/SIRT1,IL-1β and TNF-α(P<0.05),while downregulated protein expression of Occludin.Compared with LPS group,niclosamide-pretreatment downregulated protein expressions of S100A4,STAT3,MAPK3/SIRT1,IL-1β and TNF-α(P<0.05),while restored protein expression of Occludin(P<0.05).Conclusion:Calcium-binding protein S100A4 inhibitor Niclosamide can alleviate S100A4 expression and inflammatory response of bronchial epithelial cells,which is poten-tially related to STAT3 or MAPK3/SIRT1 signaling.
