Abstract Title:

Berberine induces dendritic cell apoptosis and has therapeutic potential for rheumatoid arthritis.

Abstract Source:

Arthritis Rheum. 2010 Dec 15. Epub 2010 Dec 15. PMID: 21162100

Abstract Author(s):

Zhenlin Hu, Qing Jiao, Jieping Ding, Fang Liu, Runhui Liu, Lei Shan, Huawu Zeng, Junping Zhang, Weidong Zhang

Article Affiliation:

School of Pharmacy, Second Military Medical University, Shanghai 200433, China.

Abstract:

OBJECTIVE.: To investigate the effects of berberine (Ber) on dendritic cell (DC) apoptosis and its therapeutic potential for rheumatoid arthritis (RA). METHODS.: Bone marrow (BM)-derived conventional myeloid DCs (cDCs) and plasmacytoid DCs (pDCs) were generated by culturing BM cells with GM-CSF/IL-4 or Flt3L, respectively. Splenic DCs, T and B cells were purified using MACS system. In vitro apoptosis was examined by annexin V/PI or Hoechst 33258 staining. The in vivo effects of Ber were examined in type II collagen (CII)-induced arthritic (CIA) mice. The immune responses against CII were determined by assays of serum antibody levels, lymphocyte proliferation, and cytokine production. The proportions of DCs and apoptosis of different immune cell subsets in spleens and lymph nodes were analyzed by flow cytometry and immunohistochemistry after subset-specific surface marker labeling and TUNEL staining. RESULTS.: Exposure of cDCs to Ber during BM cell differentiation reduced cell recovery by inducing apoptosis. The sensitivity to Ber-induced apoptosis was acquired from day 3 of DC differentiation onward, and mature DCs were more sensitive to Ber than immature DCs. Murine peritoneal macrophages, Raw264.7 cells, and Jurkat cells were insensitive to Ber-induced apoptosis. Splenic DCs were more sensitive to Ber than T and B cells. The pDCs showed a similar susceptibility to Ber-induced apoptosis as cDCs. In CIA mice, Ber treatment ameliorated arthritis, suppressed CII-specific immune responses, and selectively increased the incidence of apoptosis in DCs within spleens and lymph nodes. CONCLUSION.: Ber selectively induces apoptosis in DCs and may represent a novel therapeutic agent for RA.

Study Type : In Vitro Study

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