N,N-Diethylacetamide and N,N-Dipropylacetamide inhibit the NF-kB pathway in in vitro, ex vivo and in vivo models of inflammation-induced preterm birth
Abstract Preterm birth (PTB) occurs in 10% of births worldwide and remains the leading cause of neonatal morbidity and mortality. Previously, we reported that N, N-dimethylacetamide (DMA) and N, N-dimethylformamide (DMF) prevent inflammation-induced PTB in a murine model and inhibit the NF-κB inflam...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-16076-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract Preterm birth (PTB) occurs in 10% of births worldwide and remains the leading cause of neonatal morbidity and mortality. Previously, we reported that N, N-dimethylacetamide (DMA) and N, N-dimethylformamide (DMF) prevent inflammation-induced PTB in a murine model and inhibit the NF-κB inflammatory pathway. Using in vitro and ex vivo models, we show here that two DMA analogs, N,N-diethylaceatmide (DEA) and N, N-dipropylacetamide (DPA), attenuate LPS-stimulated increased secretion of tumor necrosis factor (TNF)-α, IL-6, IL-1, GM-CSF, MCP-1 and IL-10 from RAW 264.7 cells; IL-6, IL-8 and MCP-1 from HTR-8/SVneo cells; and TNF-α, IL-6, GM-CSF, IL-8, MCP-1 and IL-10 from human placental explants. In addition, both analogs inhibited LPS induced up-regulation of nitric oxide (NO) secretion and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. Further, both analogs, at 10 mM, inhibited LPS-induced degradation of IkB-⍺ in RAW 264.7 cells, leading to inhibition of the NF-kB pathway. We also found that both analogs inhibited LPS-stimulated NF-kB transcriptional activity but did not affect AP-1 or C/EBP activity. However, neither analog had any effect on the expression of native or phosphorylated forms of JNK1, ERK1/2 and p-38 MAPK. Finally, in a well-established in vivo model of preterm birth, DEA, at 750 mg/kg, prevented preterm birth for at least 24 h. DEA and DPA have potential as novel therapeutic agents for the prevention of inflammation-induced preterm birth and other inflammatory disorders. |
|---|---|
| ISSN: | 2045-2322 |