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.
Muñoz
E
E
Department of Pathology, Tufts University School of Medicine, Boston, MA 02111.
Beutner
U
U
Zubiaga
A
A
Huber
B T
BT
D000818:Animals; D015152:Blotting, Northern; D002451:Cell Compartmentation; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D017472:Receptors, Interleukin-1; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D007375:Interleukin-1; D015848:Interleukin-5; D010750:Phosphoproteins; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D015847:Interleukin-4; D000242:Cyclic AMP; D011493:Protein Kinase C