Enhancement of B-cell translocation gene-1 expression by prostaglandin E₂ in macrophages and the relationship to proliferation

Although prostaglandin (PG) E₂ is known to suppress various macrophage functions, the molecular mechanisms by which that occurs are largely unknown. To understand better those mechanisms, differential screening of a cDNA library from PGE₂-treated macrophages was performed. Subsequently, the DNA sequence of a differentially expressed cDNA clone was determined and the cDNA was identified as B-cell translocation gene-1 (BTG1), a recently cloned antiproliferative gene. A two- to threefold increase in macrophage BTG1 expression was observed after PGE₂ treatment. PGE₁ and platelet-activating factor, but not leukotrienes B₄, and C₄, or lipopolysaccharide, also enhanced BTG1 expression. Furthermore, this effect was mimicked by dibutyryl cAMP which indicated the involvement of elevated cAMP in the PGE₂-mediated enhancement of BTG1. Moreover, there was an inverse correlation between BTG1 mRNA expression and macrophage proliferation; however, BTG1 alteration was not associated with macrophage tumoricidal activation. Thus, BTG1 may play a role in PGE₂-mediated inhibition of macrophage proliferation and not activation.