Cytokine Expression in Rat Colon During Postnatal Development

Abstract

Cytokine expression and regulation by glucocorticoids and retinoic acid were investigated in the colon during postnatal development. Gene expression of the transforming growth factors (TGFs) TGF-beta1, TGF-beta2 and TGF-alpha and the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) in rat colon mucosa during weaning and in adult rats. Protein expression and distribution of TGF-betas was analysed in the colon from 14- and 60-day-old animals. The effect of hydrocortisone administration on mucosal cytokine transcripts (RT-PCR) and of dexamethasone on the expression of cytokines by the epithelial cell line IEC-18 and 2 subepithelial myofibroblasts (MIC 307-1 and 316) was examined. TGF-beta1 and TGF-beta2 messenger RNAs and proteins decreased in the entire colon from weaning to adult stages, whereas the amount of TGF-alpha messenger RNA increased in the proximal colon and decreased in the distal part of the colon in adult rats in comparison with weanlings. However, proinflammatory cytokines showed no postnatal changes in the proximal colon but decreased in the distal part in comparison with weaning rats. Hydrocortisone treatment did not affect growth factor expression but decreased proinflammatory cytokines. Likewise, dexamethasone decreased TNF-alpha and IL-1beta gene expression but did not affect TGF-betas in either epithelial or myofibroblast cells. During postnatal maturation, the expression of growth factors and proinflammatory cytokines decreased in the distal colon, whereas in the proximal colon, a differential maturation occurs with no changes in proinflammatory cytokines, an increase in TGF-alpha and a decrease in TGF-beta. Glucocorticoids may control the developmental profile of proinflammatory cytokines.