Am. J. Respir. Cell Mol. Biol., Volume 18, Number 5, May, 1998 631-642

Interleukin-5 mRNA Stability in Human T Cells Is Regulated Differently than Interleukin-2, Interleukin-3, Interleukin-4, Granulocyte/Macrophage Colony-stimulating Factor, and Interferon-

Shelby P. Umland, Shad Razac, Himanshu Shah, D. Kyle Nahrebne, Robert W. Egan, and M. Motasim Billah

Schering-Plough Research Institute, Kenilworth, New Jersey

Interleukin-5 (IL-5) transcriptional activation and mRNA stability were investigated in a human T_H0 T-cell clone (SP-B21) and in nonclonal CD4 T_H2 cells, differentiated in vitro from peripheral blood T cells. Cells were stimulated with -CD3 monoclonal antibody (mAb) with and without -CD28 mAb. Comparison to other cytokine genes revealed aspects of mRNA regulation unique to IL-5. The half-life (t_1/2) of IL-5 mRNA, determined by addition of actinomycin D (ActinoD) or cyclosporin A (CSA) was longer (by  2 h) than that of IL-2, IL-3, IL-4, interferon-, or granulocyte/macrophage colony-stimulating factor. With the exception of IL-5, t_1/2 values were significantly shorter with CSA as the transcriptional inhibitor than with ActinoD. The t_1/2 value of IL-5 mRNA, but not the other cytokine transcripts, determined with either ActinoD or CSA, was longer than predicted from the kinetics of steady-state mRNA decline. Co-stimulation of both cell types with -CD28 mAb increased the stability of cytokine transcripts weakly, and IL-5 remained the most stable transcript. Thus, the degradation pathway that targets IL-5 is distinct from the other cytokine transcripts measured and involves proteins whose transcription is blocked by ActinoD and CSA. From examination of the levels of transcription initiation (nuclear run-on assay) and steady-state mRNA attained in cultures stimulated in the presence of the protein synthesis inhibitor, cycloheximide, only IL-5 transcription initiation had an absolute dependency on new protein synthesis.

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