Calcitriol reverses sepsis-induced immunosuppression via VDR/Ca2+/pyroptosis signaling pathway
- VernacularTitle:骨化三醇通过VDR/Ca2+/细胞焦亡信号通路逆转脓毒症免疫抑制
- Author:
Shenglan SHANG
1
;
Shuo ZOU
1
;
Yuqi WEI
2
;
Mengchen YU
3
;
Fan ZHOU
3
;
Yan ZHAO
3
;
Airong YU
3
Author Information
1. School of Medicine，Wuhan University of Science and Technology，Wuhan 430065，China;Dept. of Clinical Pharmacy，General Hospital of Central Theater Command of PLA，Wuhan 430070，China
2. Dept. of Clinical Pharmacy，General Hospital of Central Theater Command of PLA，Wuhan 430070，China;School of Pharmacy，Hubei University of Science and Technology，Hubei Xianning 437100，China
3. Dept. of Clinical Pharmacy，General Hospital of Central Theater Command of PLA，Wuhan 430070，China
- Publication Type:Journal Article
- Keywords:
calcitriol;
sepsis;
immunosuppression;
pyroptosis;
Ca2+
- From:
China Pharmacy
2025;36(18):2232-2237
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of calcitriol on sepsis-induced immunosuppression and its potential mechanism. METHODS A sepsis-induced immunosuppression mice model was established using cecal ligation and puncture （CLP）. The 7-day survival rate， serum levels of tumor necrosis factor- α （TNF- α）， interleukin-6 （IL-6）， and IL-1β were determined in sham operation group， CLP group and calcitriol group （1 μg/kg）； the morphological changes of lung tissue in mice were observed. Lipopolysaccharide （LPS） tolerance macrophage models （representing sepsis-induced immunosuppression） were established using mice macrophage cell line RAW264.7 cells. The levels of TNF-α and IL-6 in cell supernatants as well as mRNA expressions of IL-1β， nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， IL-18 and caspase-1 were assessed in culture medium group， LPS group， LPS tolerance group， and calcitriol （5 μmol/L） group. The following parameters were measured： propidium iodide （PI）-positive cell ratio， caspase-1 activity， lactate dehydrogenase （LDH） release， and Ca2+ levels. RESULTS Compared with CLP group， 7-day survival rate and serum levels of TNF-α， IL-6 and IL-1β were increased significantly in calcitriol group （P＜0.05）. Additionally， pulmonary tissue damage was markedly attenuated in calcitriol group. Compared with LPS tolerance group， the levels of TNF-α and IL-6 in cell supernatants， mRNA expressions of IL- 1β， NLRP3， IL-18 and caspase-1， PI-positive cell ratio， caspase-1 activity， LDH release， and Ca2+ levels were all increased significantly in calcitriol group （P＜0.05）. CONCLUSIONS Calcitriol can reverse sepsis-induced immunosuppression， and the mechanism of action may be E-mail：yarfwy@163.com achieved by the binding of calcitriol to vitamin D receptor，which promotes the release of Ca2+ from the endoplasmic reticulum， thereby driving the NLRP3/caspase-1-mediated pyroptosis pathway.
