Functional expression of receptor activator of nuclear factor κB in Hodgkin disease cell lines

  • Paolo Fiumara
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.
  • Virginia Snell
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.
  • Yang Li
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.
  • Asok Mukhopadhyay
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.
  • Mamoun Younes
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.
  • Ann Marie Gillenwater
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.
  • Fernando Cabanillas
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.
  • Bharat B. Aggarwal
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.
  • Anas Younes
    From the Departments of Lymphoma and Myeloma, Head and Neck Surgery, and Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, and the Department of Pathology, Baylor College of Medicine, Houston, TX.

抄録

<jats:title>Abstract</jats:title><jats:p>The malignant Hodgkin and Reed-Sternberg (H/RS) cells of Hodgkin disease (HD) express several members of the tumor necrosis factor (TNF) receptor family, including CD30 and CD40, and secrete several cytokines and chemokines. However, little is known about what regulates cytokine and chemokine secretion in H/RS cells. Although H/RS cells are predominantly of B-cell origin, they frequently share phenotypic and functional features with dendritic cells (DCs). Previous studies reported that receptor activator of nuclear factor κB (NF–κB) (RANK), a member of the TNF receptor family, is expressed on DCs, and that RANK ligand (RANKL) enhances DC survival and induces them to secrete cytokines. This study reports that, similar to DCs, cultured H/RS cells expressed RANK. However, unlike DCs, H/RS cells also expressed RANKL. Soluble RANKL activated NF-κB and induced messenger RNA expression of interferon-γ, interleukin-8 (IL-8), IL-13, IL-9, IL-15, and RANTES, in addition to the receptors for IL-9, IL-13, IL-15, and CCR4. RANKL increased IL-8 and IL-13 levels in the supernatants of H/RS cell lines, an effect that was blocked by soluble RANK. Furthermore, soluble RANK decreased the basal level of IL-8 in one cell line, suggesting that IL-8 was induced by an autocrine RANKL/RANK loop. RANKL had no effect on H/RS cell survival in culture, and it did not modulate the expression of bcl-2, bcl-xL, bax, or inhibitors of apoptosis proteins. These data provide evidence of further functional similarities between DCs and H/RS cells. The coexpression of RANK and RANKL in H/RS cells suggests that they may regulate cytokine and chemokine secretion in H/RS cells by an autocrine mechanism.</jats:p>

収録刊行物

  • Blood

    Blood 98 (9), 2784-2790, 2001-11-01

    American Society of Hematology

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