期刊
SCIENCE ADVANCES
卷 7, 期 4, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd3865
关键词
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资金
- NIH/NIAID [1R21AI140249-01A1]
- UTMB
Packaging NF-kappa B inhibitor SR in exosomes provides a stable and specific intervention for reducing inflammatory response associated with PTB, prolonging gestation and reducing maternal inflammation. In a mouse model, LPS-induced PTB is associated with influx of fetal innate immune cells into feto-maternal uterine tissues.
Accumulation of immune cells and activation of the pro-inflammatory transcription factor NF-kappa B in feto-maternal uterine tissues is a key feature of preterm birth (PTB) pathophysiology. Reduction of the fetal inflammatory response and NF-kappa B activation are key strategies to minimize infection-associated PTB. Therefore, we engineered extracellular vesicles (exosomes) to contain an NF-kappa B inhibitor, termed super-repressor (SR) I kappa B alpha. Treatment with SR exosomes (1 x 10(10 )per intraperitoneal injection) after lipopolysaccharide (LPS) challenge on gestation day 15 (E15) prolonged gestation by over 24 hours (PTB <= E18.5) and reduced maternal inflammation (n >= 4). Furthermore, using a transgenic model in which fetal tissues express the red fluorescent protein tdTomato while maternal tissues do not, we report that LPS-induced PTB in mice is associated with influx of fetal innate immune cells, not maternal, into feto-maternal uterine tissues. SR packaged in exosomes provides a stable and specific intervention for reducing the inflammatory response associated with PTB.
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