Expression of Functional Interleukin-3 Receptors on Hodgkin and Reed-Sternberg Cells

Abstract

The human interleukin-3 receptor (IL-3R) is a heterodimeric complex consisting of an IL-3-specific alpha chain (IL-3Ralpha) and a common beta chain (beta(c)), this latter shared with the receptors for granulocyte-macrophage colony-stimulating factor and IL-5. Despite extensive research on cytokine circuitries regulating proliferation and survival of tumor cells in Hodgkin's disease (HD) the functional expression of IL-3Rs in this pathobiological entity has not yet been investigated. In the present study, we demonstrate that the great majority (>90%) of malignant Hodgkin and Reed-Sternberg cells of classic HD (19 of 19 analyzed cases) express IL-3Ralpha by immunostaining of frozen sections and cell suspensions from involved lymph nodes. Accordingly, HD cell lines (L428, KMH2, HDLM2, L1236) expressed the alpha and beta chains of IL-3R both at the mRNA and protein level, with a molecular size of IL-3Ralpha identical (70 kd) to that expressed by human myeloid cells. Exogenous IL-3 promoted the growth of cultured Hodgkin and Reed-Sternberg cells, such effect being potentiated by IL-9 co-stimulation, and was able to partially rescue tumor cells from apoptosis induced by serum deprivation. This data suggests an involvement of IL-3/IL-3R interactions in the cellular growth of HD through paracrine mechanisms.

Notch is an essential upstream regulator of NF-κB and is relevant for survival of Hodgkin and Reed–Sternberg cells

“…27 Similarly, IL-3 and IL-9 are functionally expressed in HRS cells and promote their proliferation. 26 Whether one of these secreted factors mediates its effects through activation of alternative NF-kB signaling in HRS cells, and whether aberrant Notch signaling might even control its expression requires further investigations.…”

“…It is known that HRS cells abundantly secrete soluble factors, such as cytokines and chemokines, and that they are involved in forming the particular microenvironment in cHL, and trigger HRS cell proliferation and survival. 14,[25][26][27] We incubated HRS cells with fresh or conditioned medium of untreated L540cy, L1236, KM-H2 and L428 cells, and simultaneously added GSI XII for 24 h. NF-kB p52 levels, which are indicative for alternative NF-kB signaling, remained stable in L540cy cells upon stimulation of cells with conditioned medium (Figure 5a, upper panel). Accordingly, conditioned medium efficiently reversed the loss of cell viability of GSI-treated HRS cells (Figure 5a, lower panel and Supplementary Figures S2A and B).…”

Probiotics Applications in Autoimmune Diseases

“…Effects on the Th1/Th2 balance have been observed in some animal models of allergy [184]; however not all strains stimulated Th1 immunity [185,186]. Nonetheless, stimulation of Th1 immunity has been reported in clinical trials [187][188][189][190][191] and clinical efficacy has been demonstrated in adults, children and infants for diseases including IBS and IBD [192,193], see Figure 4. …”

CD26 Expression Correlates with a Reduced Sensitivity to 2′-Deoxycoformycin-Induced Growth Inhibition and Apoptosis in T-Cell Leukemia/Lymphomas

“…Cell lysates from leukemia/lymphoma T-cell lines were prepared as described (33). Equal amounts of protein (50 g) were subjected to10% SDS-PAGE.…”

“…Clonogenic growth of leukemia/lymphoma T-cell lines, H9 T-cell clones, and primary leukemic T cells was assayed as described previously (2,33). Briefly, 2.0 ϫ 10 5 /ml purified tumor T cells or 5.0 ϫ 10 3 /ml T-cell lines, were suspended in 1 ml of IMDM …”