Int erleukin-1 induces c-fos and c-jun gene expression in T helper type I1 cells through different signal transmission pathways*
Interleukin (1L)-1 induces proliferation and expression of several protooncogenes in the T helper 2 cell line DlOA. We have analyzed the signal transmission pathways activated by IL-1 in these cells, leading to the expression of c-jun and c-fos. IL-1 induced c-jun gene transcription and mRNA expression by means of a pathway dependent on protein tyrosine kinase activity since tyrphostin, a specific inhibitor of tyrosine kinase, inhibited this induction. This mechanism of transmission signaling was independent of protein kinase C (PKC) and was linked to the 80-kDa IL-1 receptor (IL-1R). In addition, phorbol esters did not induce c-jun mRNA expression, whereas c-fos mRNA expression mediated by IL-1 dependent on PKC; this pathway was linked to a different, still unidentified IL-1R that was functional in the DlOA cell line. Accumulation of intracellular CAMP generated by IL-1 through the 80-kDa IL-1R negatively regulated c-fos expression which was induced by IL-1 through PKC activation.We conclude that IL-1 modulates the expression of c-fos in DlOA cells by occupying of two independent IL-1R that are linked to different signal transduction pathways.
Recently, Sims et al. [6] have cloned the murine 80-kDa IL-1R that is able to transmit signals from the cell surface to the nucleus [7]. It consists of a single polypeptide chain containing three Ig-like domains.This receptor is present in T helper type 2 (Th2) cells, as well as in fibroblasts. A second IL-1R has been cloned and codes for a 68-kDa protein that is expressed in B cells and T1,2 cells [8, 91, thus confirming data from cross-linking experiments that Th2 cells express .