IL-1 alpha induces expression of active transforming growth factor-beta in nonproliferating T cells via a post-transcriptional mechanism.
IL-1 is a co-stimulus for T cell proliferation along with TCR cross-linking agents or lectins. Here we demonstrate that IL-1 alpha, in the absence of a TCR stimulus, induces active TGF-beta production by non-proliferating T cells. Thus, in addition to being an incomplete signal, IL-1 alpha alone induced the production of a negative modulator for T cell proliferation. Interestingly, when Con A and IL-1 were combined, active TGF-beta was not detected in supernatants. Production of active TGF-beta protein by T cells in response to IL-1 alpha was established by 1) growth inhibition of the TGF-beta-responsive CCL 64 target cell, 2) neutralization of the activity in supernatants with an anti-TGF-beta mAb, and 3) competition of supernatants with [125I]TGF-beta binding to CCL 64 membranes. The mechanism of IL-1 alpha induction of TGF-beta was examined: IL-1 alpha did not increase TGF beta-1 message over constitutive levels, nor did it induce transcription of TGF-beta 2 message. A latent acid-activatable form of the protein was detected in nonproliferating murine T cells. We therefore suggest that IL-1 alpha regulates TGF-beta expression in T cells through translational and/or post-translational mechanisms. IL-1 regulation of active TGF-beta production by T cells may be a mechanism for controlling the proliferative response of T cells to a co-stimulus, and may be relevant in the pathophysiology of certain chronic inflammatory disease states.
Bristol
L A
LA
Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick, MD 21701.
Ruscetti
F W
FW
Brody
D T
DT
Durum
S K
SK
D000818:Animals; D000911:Antibodies, Monoclonal; D003208:Concanavalin A / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D003513:Cycloheximide