Colchicine-mediated microtubule (MT) disruption supports remarkable increases in LPS-stimulated transcriptional responsiveness of a GM-CSF promoter-driven reporter construct, in both B-cell (M12.4.1) and macrophage (RAW) cell lines. The present study was undertaken to elucidate whether cell type-specific mechanisms regulate the response of the GM-CSF gene to microtubule disruption. Colchicine independently enhances transcriptional potential of the murine GM-CSF promoter in both cell types and minimally requires a 60 base pair stretch of DNA sequence upstream of the transcript initiation site in the gene. This minimal GM-CSF promoter harbors the conserved lymphokine element 0 (CLE0) which contains an AP-1 site abutting a purine-rich sequence, is capable to respond to both LPS and colchicine in RAW cells, but is incapable of responding to LPS alone in M12.4.1 cells. Treatment of either cell type with colchicine activates proteins of the AP-1 (c-Jun, Jun B, Jun D, c-Fos, Fra-2) and CREB/ATF families, in both M12.4.1 and RAW cells. Transient over-expression of dominant negative versions of the ATF-2, CREB and c-Fos proteins diminishes the effect of colchicine on GM-CSF (0.2 kb) minimal promoter activity. MT disruption has opposing effects on LPS-stimulated GM-CSF mRNA and protein synthesis however, causing a dramatic increase versus decrease in B-cells and macrophages, respectively. These observations lead to the conclusion that cell type-specific post-transcriptional mechanisms may regulate the overall response of the GM-CSF gene to microtubule disruption
