Trichloroethylene (TCE) is a common organic solvent which can cause TCE hypersensitivity syndrome (THS) in exposure workers. THS is an adverse skin disorder with severe inflammatory kidney damage. Complement C3a receptor (C3aR) acts as a specific receptor for the key complement cleavage product C3a and involves multiple inflammatory responses, but the role of C3aR in TCE induced kidney inflammatory injury remains unknown. In this study, BALB/c mouse model of skin sensitization induced by TCE was set up in the presence or absence of C3aR antagonist (C3aRA). Kidney pathology and renal function, expression of inflammatory mediators and C3aR, changes in Th17 cell numbers, and activation of signal transducer and activator of transcription 3 (STAT3) in the kidney were examined. TCE sensitization produced histopathological and functional damage to the kidney, accompanied by increased levels of interleukin (IL-) 1β, IL-6, and IL-23. Local accumulation of Th17 cells and enhanced phosphorylation of STAT3 were also seen in the impaired kidney in TCE sensitization-positive mice. C3aR was mainly located in the impaired glomerulus and upregulated in TCE sensitization-positive mice. C3aRA pretreatment alleviated the structural and functional kidney damage and the inflammatory cytokine and Th17 responses by TCE sensitization, and specifically reduced the phosphorylation of STAT3. Together, our results demonstrate that C3aR signaling promotes the inflammatory responses and regulates the accumulation of Th17 phenotype via phosphorylation of STAT3 in TCE sensitization induced inflammatory kidney damage. C3aR may serve as a potential therapeutic target in TCE sensitization mediated kidney injury.
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http://dx.doi.org/10.1016/j.ecoenv.2019.109772 | DOI Listing |
Toxicol Ind Health
February 2025
Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, China.
Int Immunopharmacol
December 2024
Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei 230032, Anhui, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230032, Anhui, China; Institute of Dermatology, Anhui Medical University, Hefei 230032, Anhui, China. Electronic address:
Occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) represents a critical clinical issue, with patients frequently experiencing multi-organ damage, including renal impairment. The underlying mechanisms, however, remain elusive. This study investigated how trichloroethylene (TCE) sensitization-induced tumor necrosis factor alpha (TNF-α) deposition in renal vascular endothelial cells affects apoptosis and its underlying mechanisms.
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October 2024
Department of Breast Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530000, China.
Cold exposure (CE) therapy can quickly induce tumor starvation by brown adipose tissue (BAT) thermogenesis. Exploring the combined antitumor mechanism of CE and traditional therapies (such as radiotherapy (RT)) is exciting and promising. In this study, we investigated the effect of CE in combination with nitric oxide (NO) gas therapy on sensitizing tumors to RT and promoting tumor radio-immunotherapy.
View Article and Find Full Text PDFEcotoxicol Environ Saf
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Department of Dermatology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, China. Electronic address:
Trichloroethylene (TCE) is a common environmental contaminant that can induce occupational dermatitis medicamentosa-like TCE (ODMLT), where the liver damage is the most common complication. The study aims to uncover the underlying mechanism of TCE-sensitization-induced liver damage by targeting specific exosomal microRNAs (miRNAs). Among the enriched serum exosomal miRNAs of ODMLT patients, miR-205-5p had a significant correlation coefficient with the liver function damage indicators.
View Article and Find Full Text PDFInt Immunopharmacol
September 2024
Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, PR China; Key Laboratory of Dermatology, Ministry of Education, The First Affiliated Hospital of Anhui Medical University, Hefei, PR China. Electronic address:
In specific pathological conditions, addressing liver injury may yield favorable effects on renal function through the phenomenon of liver-kidney crosstalk. Mitochondrial DNA (mtDNA) possesses the capability to trigger downstream pathways of inflammatory cytokines, ultimately leading to immune-mediated organ damage. Consequently, understanding the intricate molecular mechanisms governing mtDNA involvement in diseases characterized by liver-kidney crosstalk is of paramount significance.
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