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Rosmarinic Acid Induces Apoptosis of Activated T Cells from Rheumatoid Arthritis Patients via Mitochondrial Pathway

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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.

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Abbreviations

RA:

rheumatoid arthritis

RosA:

rosmarinic acid

CII:

type II collagen

RANKL:

receptor activator of NF-κB ligand

FasL:

Fas ligand

MMP:

mitochondrial membrane potential

BA:

bongkrekic acid.

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ACKNOWLEDGMENTS

This work was supported by the Green Cross Corp. and by the Korean Ministry of Science and Technology under Grant CBM2-A500-001-1-0-0.

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Authors and Affiliations

  1. Division of Immune Regulation, Mogam Biotechnology Research Institute, Yongin City, Gyounggi-do, South Korea

    YUN-GYOUNG HUR, SUNGJOO KIM & JONGHWA WON

  2. Rheumatology, Arthritis Center, School of Medicine, Ajou University, Suwon City, Gyounggi-do, South Korea

    CHANG-HEE SUH

  3. Mogam Biotechnology Research Institute, 341 Bojung-dong, Giheung-gu, Yongin City, Gyounggi-do, 446-799, South Korea

    JONGHWA WON

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  1. YUN-GYOUNG HUR
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HUR, YG., SUH, CH., KIM, S. et al. Rosmarinic Acid Induces Apoptosis of Activated T Cells from Rheumatoid Arthritis Patients via Mitochondrial Pathway. J Clin Immunol 27, 36–45 (2007). https://doi.org/10.1007/s10875-006-9057-8

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