Abstract
Abstract Previous investigations have revealed the presence of a norepinephrine/β2-adrenergic receptor/cAMP/PKA-dependent mRNA decay system in T lymphocytes. The Fox family of transcription factors has been implicated in regulating lymphocyte physiology. Foxm1b is reported to be a master gene related to cellular proliferation and Foxo1 has been associated with the suppression of proliferation and promotion of apoptosis. Therefore, we explored whether a PKA-selective cAMP analogue (8Br-cAMP) and NE could regulate BALB/c murine thymocyte cell lines, S49wt and S49kin- (PKA deficient), by affecting the genetic expression of Foxm1b and Foxo1. Real-time PCR studies revealed a 2–3 fold upregulation of Foxo1 mRNA in S49wt, but not kin- cells with 150uM NE or 600uM cAMP as early as 2 hrs after treatment. Foxm1b mRNA was downregulated in S49wt cells by greater than 2 fold by 8Br-cAMP after 6 hrs (at 24 hrs). Treatment with an Epac-selective cAMP (500uM) analogue resulted in no change in Foxo1 or Foxm1b expression in S49 wt or S49 kin- cells. These results associate PKA in modulating both increased Foxo1 mRNA expression and decreased Foxm1b expression and consequent fox gene-mediated regulation of lymphocyte physiology. Supported by NIH.
Published Version
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