IL-1 activates two separate signal transduction pathways in T helper type II cells.

We have investigated the signal transduction pathways mediated by IL-1 in the Th 2 cell line D10.A, and we have made the following findings. Interaction of IL-1 with its receptor leads to the translocation of protein kinase C (PKC) from the cytosol to the membrane, phosphorylation of the 80-kDa protein that is substrate for PKC, as well as an increase in the level of cAMP. In addition, IL-1 induced IL-5 mRNA expression in these cells. We have established that the IL-5 gene is activated in D10.A cells in response to either phorbol esters or 8-Br cAMP, and that the two agents act as cofactors. IL-1 is able to synergize with phorbol esters and is additive with 8-Br cAMP for IL-5 mRNA expression. There are two possibilities to explain these results: 1) D10.A cells express two types of functional IL-1R, each linked to an independent signal transduction pathway; or 2) these cells have only one kind of IL-1R which, upon ligand interaction, mediates the activation of both the PKC and the adenylate cyclase pathway.