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

The malignant Hodgkin and Reed-Sternberg (H/RS) cells of Hodgkin disease (H D) express several members of the tumor necrosis factor (TNF) receptor fami ly, including CD30 and CD40, and secrete several cytokines and chemokines. However, little is known about what regulates cytokine and chemokine secret ion in H/RS cells. Although H/RS cells are predominantly of B-cell origin, they frequently share phenotypic and functional features with dendritic cel ls (DCs). Previous studies reported that receptor activator of nuclear fact or kappaB (NF-kappaB) (RANK), a member of the TNF receptor family, is expre ssed on DCs, and that RANK ligand (RANKL) enhances DC survival and induces them to secrete cytokines. This study reports that, similar to DCs, culture d H/RS cells expressed RANK. However, unlike DCs, H/RS cells also expressed RANKL. Soluble RANKL activated NF-kappaB and induced messenger RNA express ion of interferon-gamma, interleukin-8 (IL-8), IL-13, IL-9, IL-15, and RANT ES, in addition to the receptors for IL-9, IL-13, IL-15, and CCR4. RANKL in creased IL-8 and IL-13 levels in the supernatants of H/RS cell lines, an ef fect 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, o r inhibitors of apoptosis proteins. These data provide evidence of further functional similarities between DCs and H/RS cells. The coexpression of RAN K and RANKL in H/RS cells suggests that they may regulate cytokine and chem okine secretion in H/RS cells by an autocrine mechanism. (C) 2001 by The Am erican Society of Hematology.