Tauroursodeoxycholic Acid Alleviates Lipopolysaccharide-induced Inflammatory Injury by Modulating Endoplasmic Reticulum Stress
LIAO Huiyun
FANG Yao
LI Maoling
MENG Beibei
TANG Qiong
WU Yanwen
LIU Haichao
HU Zhenhong
Abstract：Objective To investigate the effect of endoplasmic reticulum stress(ERS)inhibitor taurour-sodeoxycholic acid(TUDCA)on the inflammatory re-sponse induced by lipopolysaccharide(LPS).Methods RAW 264.7 mouse macrophages were divided into the following groups based on different intervention factors:control group(cell cultured in complete medium),LPS group(1 μg/ml LPS treatment),different concentrations of TUDCA group(100,200,500 μmol/L TUDCA treatment),TUDCA+LPS group(100,200,500 μmol/L TUDCA+1 μg/ml LPS treatment),tunicamycin(TM)group(5 mg/L TM treatment)and TM+LPS group(5 mg/L TM+1 μg/ml LPS treatment).After the intervention,the cell survival rate were assessed using the cell counting kit 8(CCK8);the levels of nitric oxide(NO),interleukin 1 beta(IL-1β),interleukin 6(IL-6)and tumor necrosis factor alpha(TNF-α)were meas-ured by enzyme-linked immunosorbent assay(ELISA);real-time reverse transcription polymerase chain reaction(RT-PCR)and Western blot were employed to detect the mRNA and protein expressions of key signaling molecules in the ERS signaling pathway,including protein kinase-like endoplasmic reticulum kinase(PERK),activated transcription factor 6(ATF6),inositol-requiring enzyme 1 alpha(IRE1α)/X-box binding protein 1(XBP1),binding immunoglobulin protein(BIP)and C/EBP homologous protein(CHOP);additionally,the structural changes in the endoplasmic reticulum were observed using transmission electron microscopy;and cell apoptosis was evaluated terminal deoxynucl neotidyl transfer-ase-mediated dUTP nick end-labeling(TUNEL)staining.Results Compared with the control group,there was no sig-nificant difference in cell survival rate among TUDCA groups with different concentration(all P＞0.05),while the cell survival rate of TUDCA+LPS group was significantly higher than LPS group(P＜0.05).Compared with the control group,the macrophages in the LPS group showed polarization,intracellular endoplasmic reticulum expansion and autoph-agosome formation,and the levels of NOx IL-1β,IL-6 and TNF-α in the LPS group significantly increased(all P＜0.05).Compared with the control group,the cell apoptosis rate of LPS group increased;compared with the LPS group,the cell apoptosis rate in the TUDCA+LPS group significantly decreased(P＜0.05).Compared with the LPS group,the auto-phagosome formation and the lumen of endoplasmic reticulum were reduced in the TUDCA+LPS group.Compared with the control group,the mRNA and protein relative expression levels of BIP,CHOP,PERK,ATF6 and XBP1 in the LPS and TM groups significantly increased(all P＜0.001).Compared with TM+LPS and LPS groups,the mRNA and pro-tein expression levels of BIP,CHOP,PERK,ATF6 and XBP1 significantly decreased in TUDCA+LPS group(all P＜0.001).Conclusion TUDCA can protect cells from LPS-induced inflammatory injury by regulating ERS.
Keywords：Chronic airway inflammatory diseasesTauroursodeoxycholic acidLipopolysaccharideEndoplasmic reticulum stressInflammation
Publication Date：2025-08-28
Online Publishing Date：2025-09-18(First online date of this platform, not the publication date of the document)
Pages：7( 645-651 )