Journal
IMMUNOLOGY
Volume 143, Issue 4, Pages 651-660Publisher
WILEY-BLACKWELL
DOI: 10.1111/imm.12346
Keywords
epigenetic; prenatal glucocorticoid; tumour necrosis factor-
Categories
Funding
- National Science Council, Taiwan [CMRPG8B0141, CMRPG8B0142, CMRPG8C0171, NSC 102-2314-B-182A-042-MY3]
Ask authors/readers for more resources
Glucocorticoid (GC) is often given when preterm delivery is expected. This treatment is successful in stimulating the development of the fetal lung. However, reports and related research regarding the prolonged effects of prenatal GC on the development of immunity are very limited. Some data, derived from infants whose mothers were given immunosuppressants during pregnancy for the treatment of autoimmune disorders, suggest that prenatal exposure to GC may have only a limited effect on the development of the immune system. What is unknown is whether the immune modulation effects of prenatal GC might appear at a later childhood stage and beyond. Here we evaluated the immune programming influenced by prenatal GC. Pregnant Sprague-Dawley rats received dexamethasone (DEX; 01mg/kg/day) or saline at gestational days 14-20. Male offspring were killed at day 7 or day 120 after birth. Spleens were collected for immune study. Of the inflammation mediators, matrix metalloproteinase-9, tumour necrosis factor- (TNF-) and granulocyte-macrophage colony-stimulating factor mRNAs decreased in the prenatal DEX group at an early stage after birth. Upon concanavalin A stimulation, prenatal DEX treatment reduced TNF- production, but not interferon- production, by splenocytes at day 120 after birth compared with the vehicle group. Decreased levels of active chromatin signs (acetylation of histone H3 lysines, H3K4me1/3, and H3K36me3) in TNF- promoter were compatible with the expressions of TNF-. Our results suggest that prenatal DEX has a profound and lasting impact on the developing immune system even to the adult stage. Epigenetic histone modifications regulate TNF- expression following prenatal DEX in rats.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available