Expression and responsiveness of human interleukin-18 receptor (IL-18R) on hematopoietic cell lines

Interleukin-18 (IL-18) is a new inflammatory cytokine sharing biological functions with IL-12. The human IL-18 receptor (IL-18R) was recently identified and was found to be expressed on normal peripheral blood lymphocytes. To further characterize IL-18R, we analyzed IL-18R expression using a series of human hematopoietic cell lines selected from various cell lineages. We found the IL-18R expression on cells of T and B lineages as expected from analysis on normal cells. The IL-18R expression, however, was found not to be restricted to any specific maturation stages of T and B cells. In addition, we detected IL-18R expression in myeloid, monocytoid, erythroid and megakaryocytic cell lines, indicating that normal counterparts of these cell lineages could express IL-18R and participate in in vivo reactions caused by IL-18. Biochemical studies showed that IL-18R proteins exist as heterogeneous molecules ranging from 60 to 110 kDa. Deglycosylation experiments indicated that the heterogeneity could not be explained only by a difference in glycosylation. We also found that tumor necrosis factor-alpha (TNF-alpha) modulated the IL-18R expression, which implies an important in vivo effect of TNF-alpha on IL-18-induced reaction. Analyzing the responsiveness of IL-18R, we found that only KG-1 responded to IL-18 stimulation. This suggests that certain inhibitory mechanisms of IL-18 responsive genes are involved in the all IL-18R-positive cell lines except KG-1.