Comparison of IL-1α effectiveness in activating murine pre-B and T cell lines

Abstract

Interleukin-1 (IL-1) is a potent agent that induces a wide range of biological effects. The action of IL-1 is mediated by surface IL-1 receptors (IL-1R). Two types of IL-1 receptors have been identified in lymphocytes. In this study we examined activity of IL-1α in two murine lymphocyte lines that express different types of IL-1 receptors. The T lymphoid cell line EL-4 6.1 C10 expresses type I IL-1R that mediates IL-1α-induced IL-2 gene expression and secretion of IL-2. The pre-B lymphoid cell line 70Z/3 was previously shown to express type II IL-1R and responds to IL-1α by expressing immunoglobulin κ light chain mRNA and increased levels of surface IgM. We found that IL-1α was as potent in inducing IgM expression in 70Z/3 cells as it was in inducing IL-2 secretion in EL-4 6.1 C10 cells. Likewise, the IL-1α concentration sufficient to trigger κ light chain gene expression in 70Z/3 cells was similar to the concentration of IL-1α sufficient to trigger IL-2 gene expression in EL-4 6.1 C10. In both cell lines, IL-1α activated NF-κB-like DNA-binding activity but in EL-4 6.1 C10 cells the IL-1α concentration sufficient to induce NF-κB response was 1000-fold lower than in 70Z/3 cells. Monoclonal antibody, mAb M15, to the type I IL-1R blocked IL-1-induced responses in EL-4 6.1 C10 cells. Surprisingly mAb M15 also blocked IL-1 action in 70Z/3 cells, even though these cells predominantly express type II IL-1R. 15% of the total IL-1 binding sites in 70Z/3 cells were recognized by mAb M15. Human IL-1 receptor antagonist (IL-1ra), which binds to the natural murine type I but not the type II IL-1R, blocked IL-1α responses in EL-4 6.1 C10 and 70Z/3 cells. Although at low levels, Northern blot analysis confirmed that 70Z/3 cells express low levels of type I IL-1R mRNA. Taken together, these results suggest that type I IL-1R are expressed and transduce IL-1 signals in both 70Z/3 and El-4 6.1 C10 cells.