Prednisone Pathway


Prednisone is a synthetic glucocorticoid that is used clinically for its anti-inflammatory properties. Prednisone is converted to the active metabolite prednisolone in the liver. Prednisolone can diffuse passively across the cell membrane, where it binds to glucocorticoid receptors in the cytoplasm. Upon binding, the glucocorticoid receptor (GR) dissociates from heat shock protein 90, and translocate into the nucleus. In the nucleus, GR dimers can bind to glucocorticoid response element (GRE) in the promoter region of anti-inflammatory genes, which activates their transcription. GRs also inhibit transcription of inflammatory mediators by binding to negative GRE (nGRE). GRs further interact with the transcription factors cAMP-responsive element binding protein and NF-kappa-B, and inihibit their activation of inflammatory gene transcription. GRs also recruit histone deacetylase 2 to inflammatory genes, which leads to DNA condensation at those loci, thus suppressing expression of those genes.

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References

  1. Barnes, P.J., and Adcock, I.M. (2009). Glucocorticoid resistance in inflammatory disease. Lancet, 373(9678), 1905-1917. PMID: 19482216
  2. Frey, BM., and Frey, F.J. (1990). Clinical pharmacokinetics of prednisone and prednisolone. Clin Pharmacokinet, 19(2), 126-146. PMID: 2199128
  3. Pujolsa, L., Mullol, J., and Picado, C. (2009). Glucocorticoid receptor in human respiratory epithelial cells. Neuroimmunomodulation, 16(5), 290-299. PMID: 19571590