IL-1 signal transduction pathways. I. Two functional IL-1 receptors are expressed in T cells.
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.
Muñoz
E
E
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
Zubiaga
A M
AM
Sims
J E
JE
Huber
B T
BT
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D015870:Gene Expression; D007375:Interleukin-1 / Q000502:physiology*; D015848:Interleukin-5 / Q000235:genetics; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000235:genetics; D011971:Receptors, Immunologic / Q000502:physiology*; D017472:Receptors, Interleukin-1; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology
D007375:Interleukin-1; D015848:Interleukin-5; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D020598:Proto-Oncogene Proteins c-myb; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate