Cytokine gene expression during postnatal small intestinal development: regulation by glucocorticoids

Background-In the intestinal mucosa, numerous cytokines produced by the epi thelium, fibroblasts, and immune cells were shown to affect epithelial diff erentiation and proliferation through epithelial-mesenchymal and epithelial -immune cell interactions. To date, the importance of cytokines in postnata l development of the rat small intestine has not been established. Aim-To investigate the developmental changes in expression of mucosal cytok ines in the postnatal maturation of the rat small intestinal epithelium and their regulation by glucocorticoids (GC). Methods-Mucosal maturation was assessed by the onset of sucrase-isomaltase (SI) mRNA, analysed by in situ hybridisation. The amount of transforming gr owth factor beta 1 (TGF-beta 1), beta 2 (TGF-beta 2), tumour necrosis facto r alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and TGF-alpha was anal ysed by reverse transcription-polymerase chain reaction (RT-PCR) in mucosal extracts from weaning (14-21 days old) and adult rats, or one day after an injection of hydrocortisone (HC) in 11 day old rats. Similarly, expression of cytokines and the regulatory effect of GC were studied on cultured sube pithelial myofibroblasts cloned from postnatal jejunum and ileum cultured i n the absence or presence of dexamethasone (DX). Results-TGF-beta 1, TGF-beta 2, and IL-1 beta decreased during the third we ek of life while levels of TNF-alpha increased and TGF-alpha remained const ant. In parallel, SI transcripts increased and showed a progressive accumul ation in the apical part of the enterocytes first localised at the base of the villi from 18 days onwards. Interestingly, precocious induction of SI m RNA by HC paralleled the decrease in expression of TGF-beta isoforms and of IL-1 beta. All cytokines were expressed in the myofibroblast cell lines. I n addition, the results showed that TNF-alpha was differentially expressed in basal culture conditions and after DX stimulation in jejunal and ileal m yofibroblasts. DX decreased IL-1 beta but not the TGF-beta isoforms, simila r to that in vivo. Conclusions-This study shows that mucosal cytokines are developmentally reg ulated and chat GC are potentially involved in this regulation in parallel with maturation of the gut mucosa at weaning.