Neutrophil restraint by green tea: inhibition of inflammation, associated angiogenesis, and pulmonary fibrosis.
Neutrophils play an essential role in host defense and inflammation, but the latter may trigger and sustain the pathogenesis of a range of acute and chronic diseases. Green tea has been claimed to exert anti-inflammatory properties through unknown molecular mechanisms. We have previously shown that the most abundant catechin of green tea, (-)epigallocatechin-3-gallate (EGCG), strongly inhibits neutrophil elastase. Here we show that 1) micromolar EGCG represses reactive oxygen species activity and inhibits apoptosis of activated neutrophils, and 2) dramatically inhibits chemokine-induced neutrophil chemotaxis in vitro; 3) both oral EGCG and green tea extract block neutrophil-mediated angiogenesis in vivo in an inflammatory angiogenesis model, and 4) oral administration of green tea extract enhances resolution in a pulmonary inflammation model, significantly reducing consequent fibrosis. These results provide molecular and cellular insights into the claimed beneficial properties of green tea and indicate that EGCG is a potent anti-inflammatory compound with therapeutic potential.
Donà
Massimo
M
Department of Experimental Biomedical Sciences, Medical School of Padova, Padova, Italy.
Dell'Aica
Isabella
I
Calabrese
Fiorella
F
Benelli
Roberto
R
Morini
Monica
M
Albini
Adriana
A
Garbisa
Spiridione
S
D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003094:Collagen / Q000008:administration & dosage; D004338:Drug Combinations; D016650:Fluorescein-5-isothiocyanate / Q000633:toxicity; D006801:Humans; D007279:Injections, Subcutaneous; D007797:Laminin / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D018375:Neutrophil Activation / Q000187:drug effects; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016877:Oxidants / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D011509:Proteoglycans / Q000008:administration & dosage; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D013662:Tea
D020533:Angiogenesis Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D007797:Laminin; D016877:Oxidants; D010936:Plant Extracts; D011509:Proteoglycans; D013662:Tea; C417940:gallocatechin gallate; C059485:matrigel; D002392:Catechin; D003094:Collagen; D016650:Fluorescein-5-isothiocyanate