Inhibitory effect of (-)-epigallocatechin 3-gallate, a polyphenol of green tea, on neutrophil chemotaxis in vitro and in vivo.
The effect of (-)-epigallocatechin 3-gallate (EGCG), a major polyphenol of green tea, on neutrophil migration has been studied using multiwell-type Boyden chambers in vitro and a fluorescein isothiocyanate-labeled ovalbumin (FITC-OVA)-induced rat allergic inflammation model in vivo. EGCG inhibited rat neutrophil chemotaxis toward cytokine-induced neutrophil chemoattractant-1 (CINC-1) in a concentration-dependent manner. In addition, CINC-1-induced neutrophil chemotaxis was suppressed by the pretreatment of rat neutrophils with EGCG at the concentration over 15 microg/mL. EGCG caused concentration-dependent suppression of the transient increase in CINC-1-induced intracellular free calcium level in both rat neutrophils and rat CXC chemokine receptor 2 (CXCR2)-transfected HEK 293 cells. EGCG inhibited CINC-1 production by IL-1beta-stimulated rat fibroblasts (NRK-49F cells) and lipopolysaccharide-stimulated rat macrophages at the concentration over 50 microg/mL, a comparatively high concentration. Oral administration of EGCG (1.0 mg or 1.5 mg/rat) at 1 h before the challenge with FITC-OVA suppressed neutrophil infiltration into the air pouch (inflammatory site) in the air-pouch type FITC-OVA-induced allergic inflammation in rats. Chemokine levels in the pouch fluids, however, were not influenced by EGCG administration. The results suggest that EGCG suppressed neutrophil infiltration by a direct action on neutrophils, but not by indirect actions, including the suppression of chemokine production at the inflammatory site.
Takano
Katsuhiko
K
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan. takanok@ms.toyama-mpu.ac.jp
Nakaima
Keiko
K
Nitta
Makoto
M
Shibata
Futoshi
F
Nakagawa
Hideo
H
D000818:Animals; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D054360:Chemokine CXCL1; D018925:Chemokines / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D002392:Catechin; C045651:epigallocatechin gallate