Dhaliwal, W.; Bajaj-Elliott, M.; Kelly, P.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA9
Academic Journal
Background: In a 3 year study of an urban African population, we have explored the relationship of intestinal α defensin expression to tropical enteropathy and intestinal infection. Quantification of human defensins (HD) 5 and 6 mRNA revealed marked variation between individuals and with season. There were strong correlations with changes in mucosal architecture and diarrhoeal incidence. This suggests that environmental determinants elicit changes in mucosal α defensin mRNA. Aims: In view of the role of T cell activation in the pathogenesis of tropical enteropathy we hypothesise that HD5 and HD6 expression may be modulated by T cells. Methods: An in vitro organ culture system was developed and small intestinal biopsies from healthy adults undergoing endoscopy were stimulated with staphylococcal enterotoxin B (SEB) over the range 0.1-10 µg/ml for 8 or 24 hours. Biopsies were also cultured for 24 hour with SEB (10 pg/ml) or dexamethasone (10[sup -7] TM) or both. HD5 and HD6 mRNA was quantified by competitive RT-PCR. Results: A dose dependent decrease of up to 1.5 log mRNA transcripts/µg total RNA was observed (HD5, p < 0.01; HD6, p = 0.05) with increasing SEB. Dexamethasone abrogated the effect of SEB on mRNA levels, and dexamethasone alone increased mRNA levels to above those of controls (HD5, p = 0.03; HD6, p < 0.05). Preliminary data with pro-inflammatory cytokines also show downregulation of HD5 and HD6. Conclusions: These data suggest that T cell activation downregulares human intestinal α defensin expression and that the effects seen in tropical enteropathy are at least partly due to interactions with adaptive immune cells.


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