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Prenatal dexamethasone exposure in rats results in long‐term epigenetic histone modifications and tumour necrosis factor‐ α production decrease
Author(s) -
Yu HongRen,
Kuo HoChang,
Chen ChihCheng,
Sheen JiunnMing,
Tiao MaoMeng,
Chen YuChieh,
Chang KowAung,
Tain YouLin,
Huang LiTung
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12346
Subject(s) - immune system , dexamethasone , medicine , endocrinology , tumor necrosis factor alpha , offspring , glucocorticoid , immunology , pregnancy , prenatal stress , biology , genetics
Summary 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 S prague‐ D awley rats received dexamethasone ( DEX ; 0·1 mg/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‐ α ( TNF ‐ α ) and granulocyte–macrophage colony‐stimulating factor mRNA s decreased in the prenatal DEX group at an early stage after birth. Upon concanavalin A stimulation, prenatal DEX treatment reduced TNF ‐ α production, but not interferon‐ γ production, by splenocytes at day 120 after birth compared with the vehicle group. Decreased levels of active chromatin signs (acetylation of histone H3 lysines, H 3 K 4me1/3, and H 3 K 36me3) in TNF ‐ α promoter were compatible with the expressions of TNF ‐ α . 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‐ α expression following prenatal DEX in rats.