Regulation of perforin gene expression in a T cell hybrid with inducible cytolytic activity.
A mouse x rat T cell hybrid (PC60) that does not require interleukin (IL)-2 for proliferation, was used as a model to study regulation of perforin gene expression. Perforin mRNA is barely detectable in non-induced PC60 cells; however, a 30-fold induction is observed after stimulation with IL-1 alone. Peak perforin mRNA levels were reached after 10 h of induction with IL-1, and these levels were maintained for as long as the stimulus was present. IL-2 by itself has no detectable effect. However, in combination with IL-1 it shows the same induction kinetics as IL-1 alone for the first 10 h, subsequently there is synergism (100-fold induction) between IL-1 and IL-2. The induction response was mainly due to increased transcriptional rates of the perforin gene, and require newly synthesized proteins. The half-life of perforin mRNA in this system is about 5 h. In addition, we confirm the existence of two types of mouse perforin mRNA that differ in their 5' untranslated regions, and show evidence that both mRNA are translated in vivo with similar efficiencies.
García-Sanz
J A
JA
Department of Microbiology and Immunology, University of Miami, School of Medicine.
Podack
E R
ER
D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D006825:Hybridomas / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*; D014158:Transcription, Genetic
D007375:Interleukin-1; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D054353:Perforin