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IL-1 signal transduction pathways. I. Two functional IL-1 receptors are expressed in T cells

E Muñoz1, A M Zubiaga, J E Sims

  • 1Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.

Journal of Immunology (Baltimore, Md. : 1950)
|January 1, 1991
PubMed

We have recently characterized a subline of the Th2 cell line D10.G4.1, D10A, which responds to exogenous IL-1 in the absence of cofactors. In this cell line IL-1 activates two distinct transmission signal pathways, one leading to increased levels of intracellular cAMP, and the other to the phosphorylation of an 80-kDa substrate of protein kinase C (PKC). To determine whether both pathways are activated upon occupancy of a single IL-1R, we used a mAb, M15, which blocks binding of IL-1 to the 80-kDa IL-1R, known to be expressed in Th2 cells. Whereas M15 was able to inhibit the accumulation of cAMP induced by IL-1, it had no effect on the IL-1-induced phosphorylation of the 80-kDa substrate of PKC or the c-fos mRNA expression. In addition, we show that IL-1 induces the expression of the two proto-oncogenes c-myb and c-myc through the 80-kDa IL-1R, and that this induction is PKC independent. The proliferation of D10A cells in response to IL-1 is blocked by M15, but is unaffected by H-7, a potent inhibitor of PKC. These results indicate that the IL-1-induced proliferation of D10A cells is independent of PKC. In addition, IL-1 induces c-fos mRNA expression in thymocytes but not in EL-4 cells.

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