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Gut 47:192-198 doi:10.1136/gut.47.2.192
  • Small intestine

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

Abstract

BACKGROUND In the intestinal mucosa, numerous cytokines produced by the epithelium, fibroblasts, and immune cells were shown to affect epithelial differentiation and proliferation through epithelial-mesenchymal and epithelial-immune cell interactions. To date, the importance of cytokines in postnatal development of the rat small intestine has not been established.

AIM To investigate the developmental changes in expression of mucosal cytokines 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 growth factor β1 (TGF-β1), β2 (TGF-β2), tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β), and TGF-α was analysed 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 subepithelial myofibroblasts cloned from postnatal jejunum and ileum cultured in the absence or presence of dexamethasone (DX).

RESULTS TGF-β1, TGF-β2, and IL-1β decreased during the third week of life while levels of TNF-α increased and TGF-α remained constant. In parallel, SI transcripts increased and showed a progressive accumulation in the apical part of the enterocytes first localised at the base of the villi from 18 days onwards. Interestingly, precocious induction of SI mRNA by HC paralleled the decrease in expression of TGF-β isoforms and of IL-1β. All cytokines were expressed in the myofibroblast cell lines. In addition, the results showed that TNF-α was differentially expressed in basal culture conditions and after DX stimulation in jejunal and ileal myofibroblasts. DX decreased IL-1β but not the TGF-β isoforms, similar to that in vivo.

CONCLUSIONS This study shows that mucosal cytokines are developmentally regulated and that GC are potentially involved in this regulation in parallel with maturation of the gut mucosa at weaning.

Footnotes

  • Abbreviations used in this paper:
    GC
    glucocorticoids
    SI
    sucrase-isomaltase
    TGF
    transforming growth factor
    TNF-α
    tumour necrosis factor α
    IL-1β
    interleukin 1β
    HC
    hydrocortisone
    RT-PCR
    reverse transcription-polymerase chain reaction
    EGF
    epidermal growth factor
    DTT
    dithiothreitol
    SSC
    standard saline citrate