title: Berberine induces dendritic cell apoptosis and has therapeutic potential for rheumatoid arthritis.
abstract: OBJECTIVE
  To investigate the effects of berberine on dendritic cell (DC) apoptosis and its potential as a therapeutic agent in rheumatoid arthritis (RA).
  
  
  METHODS
  Bone marrow (BM)-derived myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) were generated by culturing BM cells with granulocyte-macrophage colony-stimulating factor/interleukin-4 or flt3L, respectively. Splenic DCs, T cells, and B cells were purified using a magnetic-activated cell sorting system. In vitro apoptosis was assessed by annexin V/propidium iodide or Hoechst 33258 staining. The in vivo effects of berberine were examined in mice with collagen-induced arthritis (CIA). Immune responses against type II collagen (CII) were determined by assaying 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 MDCs to berberine during BM cell differentiation reduced cell recovery by inducing apoptosis. Sensitivity to berberine-induced apoptosis was acquired starting on day 3 of DC differentiation, and mature DCs were more sensitive to berberine than immature DCs. Murine peritoneal macrophages, RAW 264.7 cells, and Jurkat cells were insensitive to berberine-induced apoptosis. Splenic DCs were more sensitive to berberine than T and B cells. Susceptibility of PDCs to berberine-induced apoptosis was similar to that of MDCs. In mice with CIA, berberine treatment ameliorated arthritis, suppressed CII-specific immune responses, and selectively increased the incidence of apoptosis in DCs within spleens and lymph nodes.
  
  
  CONCLUSIONS
  These findings show that berberine selectively induces apoptosis in DCs. Berberine may thus represent a novel therapeutic agent for RA.
authors.affiliation: Second Military Medical University, Shanghai, China.
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Hu
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiao
authors.forename: Jieping
authors.initials: J
authors.lastname: Ding
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Runhui
authors.initials: R
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Shan
authors.forename: Huawu
authors.initials: H
authors.lastname: Zeng
authors.forename: Junping
authors.initials: J
authors.lastname: Zhang
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000187:drug effects / Q000473:pathology
chemical_list: D018501:Antirheumatic Agents; D001599:Berberine