Title: The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine inhibits lipopolysaccharide-induced inflammation transcriptomic pathways and cytokine secretion in a macrophage cell model

Accession Number: GSE183141

Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE183141

Repository: Gene Expression Omnibus (GEO)

Data Type(s): Gene Expression

Experiment Type(s): Expression profiling by high throughput sequencing

Organism(s): Homo sapiens

Summary: Macrophage cells play a critical role in the innate immune response during infection. Previous studies have reported that the trichloroethylene (TCE) metabolite S-(1,2-dichlorovinyl)-l-cysteine (DCVC) inhibits cytokine secretion in pathogen stimulated placental membranes, but little is known about the mechanism for these effects, including which cell types or transcriptomic pathways are impacted. We tested the hypothesis that DCVC inhibits lipopolysaccharide (LPS) stimulated inflammation pathways in differentiated (macrophage like) THP-1 cells. THP-1 cells were differentiated with phorbol 12-myristate 13-acetone (PMA) for 24 h and then treated with 1, 5, or 10 uM DCVC for 24 h. After an additional 4 h incubation with lipopolysaccharide (LPS), RNA was harvested, and RNA sequencing and cytokine analysis was performed. There were 1,399 differentially expressed genes in the cells co-treated with DCVC and LPS compared to LPS alone. Major pathways impacted include the inflammatory response, response to cytokines, and leukocyte activation. Finally, DCVC significantly reduced LPS-stimulated IL-1 , IL-6, and TNF- secretion. These findings suggest that TCE could potentially modify important macrophage functions during infection.

Publication(s) associated with this dataset:

• Harris S, Bakulski KM, Dou JF, Houskamp E, Scheeres EC, Schellenboom E, Harlow O, Loch-Caruso R, Boldenow E. 2022. The trichloroethylene metabolite S-(1,2-dichlorovinyl)-l-cysteine inhibits lipopolysaccharide-induced inflammation transcriptomic pathways and cytokine secretion in a macrophage cell model. Toxicol Vitro 84:105429. doi:10.1016/j.tiv.2022.105429 PMID:35811015