IGF-1, PDGF AND CD18 ARE ADHERENCE-RESPONSIVE GENES - REGULATION DURING MONOCYTE DIFFERENTIATION

Unstimulated mononuclear cells express IGF-1, PDGF-A and PDGF-B mRNA, but not a number of other genes coding for growth factors or cytokines , as we demonstrated previously. The main focus of the present investi gation was to compare gene expression of mononuclear cells unstimulate d in suspension with gene expression of monocytes stimulated by adhere nce. mRNA levels of IGF-1-A and -B, PDGF-A, -B, PD-ECGF, basic FGF, ac idic FGF, TGF-alpha, TGF-beta 1, and IGF-2 were sought for and quantif ied with our sensitive RT-PCR method (3n-PCR). The respective mRNAs of basic FGF, acidic FGF, TGF-alpha and IGF-2 were not detected, indepen dent of the culture conditions. In suspension culture, mRNA levels of IGF-1A and -B, PDGF-A, -B, and CD18 remained unchanged. Monocyte adher ence regulated IGF-1A, PDGF-A, and -B mRNA levels. In parallel, mRNA l evels of the monocyte adhesion molecule CD18 increased rapidly (4.5-fo ld). In contrast, independent of the presence of an adherence stimulus , the mRNAs for the cytoskeletal structure protein p-actin and PD-ECGF remained constant, whereas mRNA for growth factors TGF-beta 1 and IGF -1B, respectively, was increased. Thus, monocyte adherence selectively regulates IGF-1, PDGF-A, PDGF-B and CD18 mRNAs (adherence-responsive genes) in a coordinated manner. This led us to identify two novel cons ensus elements within their respective functional promoters. Both moti fs, an 11 bp purine-rich sequence and a 13 bp pyrimidine-rich segment, respectively, are absent from the genes that were not specifically ac tivated by adherence. The identified elements are potential binding si tes for transcription factors that may define a common basis for the r egulation of the adherence-responsive genes IGF-1A, PDGF-A, PDGF-B and CD18. (C) 1998 Elsevier Science B.V.