NGFI-A gene expression is necessary for T lymphocyte proliferation.
NGFI-A is an immediate early gene, encoding a zinc finger protein, rapidly activated after mitogenic stimulation. NGFI-A gene expression was found to be rapidly and transiently induced after interleukin-2 (IL-2) stimulation of G1 lymphoblasts, as well as during the G0/G1 transition, when stimulated with concanavalin A (ConA). Activation of both Ca2+ and protein kinase C pathways, separately, in quiescent T lymphocytes produced a partial induction of this gene; however, both stimuli together are necessary to obtain a full response. ConA-induced activation of NGFI-A in quiescent cells was inhibited by immunosuppressors. 8-Bromo-cAMP was able to inhibit the expression of this gene in G1 lymphoblasts after IL-2 stimulation, but failed to interfere with the ConA-induced expression in quiescent T lymphocytes. Exposure of T cells to an NGFI-A antisense oligonucleotide blocked the ConA- and IL-2-induced proliferation of the cells, measured as thymidine incorporation and cell number. This inhibition provides direct evidence that the early gene NGFI-A plays a regulatory role in growth control processes of lymphocytes and that its expression is essential for cellular proliferation.
Perez-Castillo
A
A
Insituto Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Pipaón
C
C
García
I
I
Alemany
S
S
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects; D017874:Immediate-Early Proteins; D007376:Interleukin-2 / Q000494:pharmacology*; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D051381:Rats; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016335:Zinc Fingers / Q000235:genetics
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D007376:Interleukin-2; D016376:Oligonucleotides, Antisense; D014157:Transcription Factors; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin