Coordinate regulation of multiple human lymphokine genes by Oct-1 and potentially novel 45 and 43 kDa polypeptides

The hematologic response to inflammation is critically dependent on the release of a family of glycoproteins termed CSFs. Central to this process is the coordinated T lymphocyte production of three of these proteins, granulocyte macrophage-CSF (GM-CSF), IL-3, and IL-5. In the course of our studies of the transcriptional regulation of IL-3 expression we noted that the same or similar proteins that bound to the downstream-activating region of the human IL-3 gene were also captured using DNA probes derived from sequences present in the GM-CSF and IL-5 genes. In this study, DNA-protein cross-linking techniques and reporter gene analyses were used to define the nuclear proteins that mediate transcriptional enhancement of these genes at one cis-acting site. These studies establish that Oct-1, a member of the POU family of transcription factors, binds to regions of the GM-CSF, IL-3, and IL-5 promoters and contributes to basal T cell gene transcription. In addition, although the c-jun proto-oncogene product was detected in stimulated human T cells, two additional T cell-specific proteins (45 and 43 kDa) bind to the GM-CSF, IL-3, and IL-5 promoters and are functionally and immunologically distinct from c-jun or OAP40 (jun-D). These proteins contribute to transcriptional enhancement of the IL-3 and GM-CSF genes in stimulated T cells. Together, these data suggest that the coordinate regulation of several lymphokine genes is based on responses to shared proteins. These studies further our understanding of the networks of transcriptionally active proteins responsible for the host response to inflammatory stimuli.