Green Tea Extract Induces Interleukin-8 (IL-8) mRNA and Protein Expression but Specifically Inhibits IL-8 Secretion in Caco-2 Cells

Abstract

The chemokine interleukin (IL)-8 is a cytokine involved in neutrophil attraction and activation and elevated levels have been observed in intestinal inflammation. Anti-inflammatory activities have been attributed to green tea or its major constituent (-)-epigallocatechin gallate (EGCG). In this study, we investigated the effects of a defined green tea extract (GTE) or EGCG on basal or IL-1β-induced IL-8 expression and secretion in the human gastrointestinal epithelial cell line Caco-2. mRNA expression levels were determined by quantitative RT-PCR. GTE significantly induced IL-8 mRNA expression, which was not mediated indirectly via an induction of IL-1β mRNA expression. EGCG only exerted a weak although significant induction of IL-8 mRNA expression at the highest concentration. Intracellular and extracellular protein levels were analyzed by an enzyme-linked immunosorbent assay. GTE and EGCG significantly decreased secreted IL-8 concentrations. Determination of intracellular and secreted IL-8 concentrations after 24 h, 48 h, and 72 h of incubation suggested that GTE specifically inhibited IL-8 secretion while inducing de novo synthesis of IL-8. The IL-1β-mediated increase of IL-8 secretion was significantly inhibited by GTE in a dose-dependent manner. At the highest concentration, GTE inhibited IL-1β-induced IL-8 secretion to a similar extent as found for brefeldin A, an inhibitor of vesicular transport. These results suggest that GTE may exert an anti-inflammatory activity in enterocytes, which may be useful for the treatment of intestinal inflammation.

Key words

Green tea - Camellia sinensis (L.) O. Kuntze - Theaceae - chemokines - interleukin-8

References

• 1 Yang S K, Eckmann L, Panja A, Kagnoff M F. Differential and regulated expression of C-X-C, C-C, and C-chemokines by human colon epithelial cells.  Gastroenterology. 1997;  113 1214-23
• 2 Woywodt A, Neustock P, Kruse A, Schwarting K, Ludwig D, Stange E F. et al . Cytokine expression in intestinal mucosal biopsies. In situ hybridisation of the mRNA for interleukin-1 beta, interleukin-6 and tumour necrosis factor-alpha in inflammatory bowel disease.  Eur Cytokine Netw. 1994;  5 387-95
• 3 Papadakis K A, Targan S R. Role of cytokines in the pathogenesis of inflammatory bowel disease.  Annu Rev Med. 2000;  51 289-98
• 4 MacDermott R P, Sanderson I R, Reinecker H C. The central role of chemokines (chemotactic cytokines) in the immuno-pathogenesis of ulcerative colitis and Crohn’s disease.  Inflamm Bowel Dis. 1998;  4 54-67
• 5 Puleston J, Cooper M, Murch S, Bid K, Makh S, Ashwood P. et al . A distinct subset of chemokines dominates the mucosal chemokine response in inflammatory bowel disease.  Aliment Pharmacol Ther. 2005;  21 109-20