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- Title
Analysis of Interleukin (IL)-1β and Transforming Growth Factor (TGF)-β-Induced Signal Transduction Pathways in IL-2 and TGF-β Secretion and Proliferation in the Thymoma Cell Line EL4.NOB-1.
- Authors
SIESE; JAROS; WILLIG; Siese, Anette
- Abstract
In the present study we investigated the interleukin (IL)-1β and transforming growth factor-β1 (TGF-β1)-mediated proliferation, and production of IL-2 and TGF-β, in the murine T-cell line, EL4.NOB-1. This cell line is resistant to TGF-β concerning growth arrest but not autoinduction or suppression of IL-1-induced IL-2 production. When cocultured with IL-1β, TGF-β showed growth-promoting activity that could be antagonized by adding the phosphatidyl choline-dependent phospholipase C (PC-PLC) inhibitor, D609. Using specific enzyme inhibitors of protein kinases (PK) C and A, mitogen-activated protein kinase (MAPK), phospholipase A2 (PLA2), phosphatidylinositol-dependent (PI)-PLC and PC-PLC, we showed that IL-1β-induced IL-2 synthesis was dependent on all investigated kinases and phospholipases, except PC-PLC. TGF-β1 was able to inhibit IL-2 synthesis by the activation of PKA and MAPK. The same kinases are involved in TGF-β autoinduction that is accompanied by a secretion of the active but not the latent growth factor and is antagonized by IL-1β. Addition of the PI-PLC inhibitor, ET18OCH3, or the PLA2 inhibitor (quinacrine) alone, resulted in secretion of latent TGF-β and, in the case of ET18OCH3, active TGF-β. These data implicate a role for PI-PLC and PLA2 in the control of latency and secretion. Analysis of specific tyrosine activity and c-Fos expression showed synergistic but no antagonistic effects. These events are therefore not involved in IL-1 and TGF-β-regulated IL-2 and TGF-β production, but might participate in IL-1/TGF-β-induced growth promotion.
- Subjects
INTERLEUKIN-1; TRANSFORMING growth factors-beta; CELLULAR signal transduction
- Publication
Scandinavian Journal of Immunology, 1999, Vol 49, Issue 2, p139
- ISSN
0300-9475
- Publication type
Article
- DOI
10.1046/j.1365-3083.1999.00477.x