Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediatedby reciprocal secretion of adenosine and IL-6

Citation
Sv. Sitaraman et al., Neutrophil-epithelial crosstalk at the intestinal lumenal surface mediatedby reciprocal secretion of adenosine and IL-6, J CLIN INV, 107(7), 2001, pp. 861-869
Citations number
37
Categorie Soggetti
Medical Research General Topics
Journal title
JOURNAL OF CLINICAL INVESTIGATION
ISSN journal
00219738 → ACNP
Volume
107
Issue
7
Year of publication
2001
Pages
861 - 869
Database
ISI
SICI code
0021-9738(200104)107:7<861:NCATIL>2.0.ZU;2-9
Abstract
Adenosine is formed in the intestinal lumen during active inflammation from neutrophil-derived 5 ' AMP. Using intestinal epithelial cell line T84, we studied the effect of adenosine on the secretion of IL-6, a proinflammatory cytokine involved in neutrophil degranulation and lymphocyte differentiati on. Stimulation of T84 monolayers with either apical or basolateral adenosi ne induces A2b receptor-mediated increase in IL-6 secretion, which is polar ized to the apical (luminal) compartment. In addition, Salmonella typhimuri um, TNF-a, and forskolin, known inducers of IL-6 secretion in intestinal ep ithelial cells, also stimulate IL-G secretion into the apical compartment. We show that IL6 promoter induction by adenosine occurs through cAMP-mediat ed activation of nuclear cAMP-responsive element-binding protein (CREB). We also show that IL-6 released in the luminal (apical) compartment achieves a sufficient concentration to activate neutrophils (from which the adenosin e signal originates), since such IL-6 is found to induce an intracellular [ Ca++] flux in neutrophils. We conclude that adenosine released in the intes tinal lumen during active inflammation may induce IL-6 secretion, which is mediated by cAMP/CREB activation and occurs in an apically polarized fashio n. This would allow sequential activation of neutrophil degranulation in th e lumen - a flow of events that would, in an epithelium-dependent fashion, enhance microbicidal activity of neutrophils as they arrive in the intestin al lumen.