Rosmarinic acid induces apoptosis of activated T cells from rheumatoid arthritis patients via mitochondrial pathway.
T cells play an important role in the initiation and the progression of rheumatoid arthritis (RA) and depletion of potentially pathogenic T cells was suggested as an important therapeutic protocol. We determined if rosmarinic acid (RosA), known as a secondary metabolite from herbal plants, had apoptotic activity toward T cells from RA patients and further verified target T-cell subsets. CD3(+)CD25(+) activated T-cell subsets from most of the RA patients displayed significantly higher apoptosis rates than did the PBMCs and total CD3(+) T cells. Furthermore, activated and effector CD4(+) T cells, including CD4(+)CD25(+) and CD4(+)CD45RO(+) T cells, had a tendency of being more susceptible to RosA-induced apoptosis than that of resting and naïve T-cell subsets. RosA induced the release of cytochrome c from mitochondria and the blockage of mitochondrial depolarization inhibited apoptosis. Taken together, these results suggest that RosA induces apoptosis of activated T-cell subsets from RA patients via a mitochondrial pathway.
Hur
Yun-Gyoung
YG
Division of Immune Regulation, Mogam Biotechnology Research Institute, Yongin City, Giheung-gu, Gyounggi-do, South Korea.
Suh
Chang-Hee
CH
Kim
Sungjoo
S
Won
Jonghwa
J
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D053630:Depsides / Q000494:pharmacology*; D005260:Female; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007425:Intracellular Membranes / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000097123:Rosmarinic Acid
D017252:CD3 Complex; D002934:Cinnamates; D045304:Cytochromes c; D053630:Depsides; D053645:Interleukin-2 Receptor alpha Subunit; D000097123:Rosmarinic Acid