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

Area of Science:

• Gastroenterology
• Developmental Biology
• Molecular Biology

Background:

• Cytokines influence intestinal epithelial cell differentiation and proliferation.
• The role of cytokines in postnatal rat small intestine development is not well understood.

Purpose of the Study:

• To examine developmental changes in mucosal cytokine expression during postnatal rat small intestine maturation.
• To investigate the regulation of these cytokines by glucocorticoids (GC).

Main Methods:

• Assessed mucosal maturation via sucrase-isomaltase (SI) mRNA using in situ hybridization.
• Analyzed cytokine levels (TGF-β1, TGF-β2, TNF-α, IL-1β, TGF-α) via RT-PCR in mucosal extracts and cultured myofibroblasts.
• Investigated GC effects using hydrocortisone (HC) and dexamethasone (DX) in vivo and in vitro.

Main Results:

• TGF-β1, TGF-β2, and IL-1β decreased, while TNF-α increased during the third postnatal week; SI mRNA levels rose.
• HC administration induced SI mRNA precociously, coinciding with decreased TGF-β isoforms and IL-1β.
• Glucocorticoids differentially affected cytokine expression in jejunal and ileal myofibroblasts; DX reduced IL-1β in vitro.

Conclusions:

• Mucosal cytokines are developmentally regulated in the postnatal rat small intestine.
• Glucocorticoids appear to play a role in regulating these cytokines during gut maturation at weaning.