N,N-dimethylacetamide regulates the proinflammatory response associated with endotoxin and prevents preterm birth

Sruthi Sundaram, Charles R. Ashby, Ryan Pekson, Vaishali Sampat, Ravikumar Sitapara, Lin Mantell, Chih Hung Chen, Haoting Yen, Khushboo Abhichandani, Swapna Munnangi, Nikhil Khadtare, Ralph A. Stephani, Sandra E. Reznik

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

The proinflammatory response leads to various types of pathologic pathways, including the development of preterm birth. Preterm birth occurs in 12% of deliveries in the United States and causes more than 70% of perinatal morbidity and mortality. The most common cause of spontaneous preterm birth is intrauterine infection in the mother. There is accumulating evidence indicating that the release of proinflammatory cytokines plays a critical role in the pathogenesis of inflammation-associated premature delivery. We found that the common organic solvent, N,N-dimethylacetamide (DMA), prevents endotoxin-induced preterm birth in timed pregnant C57BL/6 embryonic day (E)15.5 mice and rescues their pups from spontaneous abortion at doses many-fold lower than those currently used clinically and in a dose-dependent fashion. We also provide histologic evidence that DMA suppresses the endotoxin-triggered proinflammatory response by significantly attenuating inflammatory cell infiltration of placental tissue. Furthermore, immunoblotting analysis of placental tissue harvested from our murine models revealed DMA-mediated regulation of expression of the proinflammatory cytokines IL-1β, tumor necrosis factor α, and IL-6, and increased expression of the regulatory inflammatory cytokine IL-10. By using in vitro studies, we provide evidence that DMA suppresses macrophage function and that this small molecule prevents nuclear translocation of nuclear factor-kB. These results suggest that DMA represents a newly discovered, nontoxic therapy for a broad range of inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)422-430
Number of pages9
JournalAmerican Journal of Pathology
Volume183
Issue number2
DOIs
Publication statusPublished - Aug 1 2013

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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