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Trichloroethylene induces immune renal tubular injury through SIRT 1/HSP 70/TLR 4 pathway in BALBc mice.
- Source :
-
International Immunopharmacology . Nov2022, Vol. 112, pN.PAG-N.PAG. 1p. - Publication Year :
- 2022
-
Abstract
- • SIRT1-mediated inflammation is involved in trichloroethylene induced renal injury. • SIRT1 down-regulation promotes HSP70 release from renal tubular epithelial cells. • SIRT1 weakens HSP70 and TLR4 interaction in trichloroethylene induced renal injury. Trichloroethylene (TCE) is a volatile chlorinated solvent widely used for cleaning and degreasing industrial metal parts. Due to the widespread use and improper disposal of TCE, exposure to TCE causes a variety of adverse effects on human and animal health. However, the underlying mechanism of the damage remains unclear. The purpose of this study is to investigate the role of Sirtuin-1 (SIRT 1) in TCE-induced immune renal tubular injury. 6–8-week-old female BALB/c mice were used to construct a TCE sensitized mouse model. SIRT 1 activator, SRT 1720 (0.1 ml, 5 mg/kg) and toll like receptor 4 (TLR 4) inhibitor, TAK-242 (0.1 ml, 3 mg/kg) were used for treatment. Results show that SIRT 1 and heat shock protein 70 (HSP 70) levels are significantly down-regulated in renal tubules, serum and urine HSP 70 levels are significantly increased, and inflammatory cytokines levels are significantly increased in renal tubules in TCE-sensitized positive mice. After SRT 1720 treatment, intracellular HSP 70 level is significantly increased and extracellular HSP 70 level is decreased, and inflammatory cytokines levels get alleviated. In addition, HSP 70 and Toll-like Receptor 4 (TLR 4) proteins exist an interaction that can be significantly attenuated by SIRT 1. Subsequently, inflammation of the renal tubules mediated by SIRT 1 downregulation is attenuated after TAK-242 treatment. In conclusion, SIRT 1 alleviates renal tubular epithelial cells immune injury by inhibiting the release of HSP 70 and thereby weakening interaction with HSP 70 and TLR 4. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 112
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 159693106
- Full Text :
- https://doi.org/10.1016/j.intimp.2022.109203