Background and Aims: The immature human gut has a propensity to exaggerated inflammatory responses which are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study is to investigate the direct role of hydrocortisone on gene expression patterns and inflammatory responses in immature human enterocytes. Methods: Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 was investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β, TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional read-out. Results and Conclusions: Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α -induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 hours prior to stimulation. Our observations provide a physiologic basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment.
- immature human intestinal epithelia
- inflammatory responses
- Copyright © 2015, American Journal of Physiology- Gastrointestinal and Liver Physiology