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 granulocytemacrophage 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.Conclusion. These findings show that berberine selectively induces apoptosis in DCs. Berberine may thus represent a novel therapeutic agent for RA.

Berberine prevents nitric oxide-induced rat chondrocyte apoptosis and cartilage degeneration in a rat osteoarthritis model via AMPK and p38 MAPK signaling

“…And the relevant mechanisms deserve further study. Third, the co-treatment of a high concentration of BBR (100 lM) and 0.75 mM SNP could enlarge the toxic effect of BBR and reveal the rare effect of BBR on promoting apoptosis according to previous study [37]. In this study, the results of flow cytometry test and Western blot have demonstrated that BBR reversed SNPinduced chondrocyte apoptosis, and down-regulated the protein expressions of Bax and caspase-3, while up-regulated Bcl-2 expression in cultured chondrocytes.…”

Piperlongumine Suppresses Dendritic Cell Maturation by Reducing Production of Reactive Oxygen Species and Has Therapeutic Potential for Rheumatoid Arthritis

“…Increasing evidence has shown that DCs may be attractive targets for the treatment of autoimmune diseases, such as RA (36,37). For instance, injection of immature DCs attenuates CIA by inducing in vivo expansion of CD49b + regulatory T cells (38).…”

Berberine Suppresses Th17 and Dendritic Cell Responses

“…BBR also suppressed the expression of costimulatory molecules in DCs, which is in agreement with earlier findings in animals, which showed that BBR was able to downregulate the expression of CD80 and CD86 in mouse DCs stimulated by LPS. 19 A downregulated expression of costimulatory molecules on DCs may partially contribute to the observed impaired T-cell reactivity. Based on the study presented here and previous studies, it becomes evident that BBR can act as a negative modulator of the Th17 cell response via an effect on APCs, especially DCs.…”

“…One of the main active ingredients of these herbs, BBR also exhibits antitumor, antimicrobial, and even antidiabetic effects. [15][16][17][18] Recent reports have suggested that BBR may suppress inflammation in collagen-induced arthritis, an animal model for human rheumatoid arthritis, 19 experimental type I diabetes, 20 and experimental autoimmune encephalomyelitis, an animal model for human multiple sclerosis. 21,22 These findings raised the question of whether BBR could possibly also be applied in the treatment for clinical autoimmune uveitis.…”