Sodium salicylate induces the expression of the immunophilin FKBP51 and biglycan genes and inhibits p34cdc2 mRNA both in vitro and in vivo.

One of the mechanisms proposed to explain the anti-inflammatory activity of sodium salicylate (NaSal) is based, at least in part, on its ability to inhibit nuclear factor-kappaB activation and inhibition of nuclear factor-kappaB-dependent gene expression. On the other hand, little is known about the ability of NaSal to activate gene expression. By differential display reverse transcription polymerase chain reaction, we identified several genes that are modulated upon treatment of mouse fibroblasts with NaSal. From the various cDNA fragments recovered from autoradiograms, we found that NaSal can increase the levels of mRNA for biglycan, the mouse homologue of the human eIF-3 p47 unit, and immunophilin FKBP51. NaSal-induced expression of these genes was time- and dose-dependent. Moreover, FKBP51 gene expression was augmented in vivo, in mice treated orally or intraperitoneally with NaSal. We also found that treating cells with NaSal can inhibit the expression of the p34(cdc2) kinase. The impact this inhibition on cell cycle was evaluated by measuring the content of DNA during the cell cycle. Treatment of cells with NaSal led to a G(2)/M arrest. By investigating the signaling events that regulate the expression of these genes and their biological activities, we can contribute to the understanding of the mechanism of NaSal.