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Pathway Description
Prednisone Anti-inflammatory Action Pathway
Homo sapiens
Drug Action Pathway
Prednisone is a corticosteroid used to treat inflammation or immune-mediated reactions and to treat endocrine or neoplastic diseases. It is indicated as an anti-inflammatory or immunosuppressive drug for allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, infectious, endocrine, or neoplastic conditions as well as in organ transplant.
It is derived from cortisone.1 It is biologically inert and converted to prednisolone in the liver by the enzyme Corticosteroid 11-beta-dehydrogenase isozyme 1.
As prednisolone is a glucocorticoid, it's mechanism of actions is that of the glucocorticoid response element of influencing COX-2/prostaglandin G/H synthase 2 suppression and lipocortin/annexin induction. By binding to the glucocorticoid receptor, it influences transcription factors AP-1 and NF-kB to block the transcription of COX-2/prostaglandin G/H synthase 2 which reduces the amount of prostanoids being produced from arachidonic acid. Prostanoids such as PGI2 and thromboxane A2 influence effects of inflammation through vasoconstriction/dilation, pain sensitivity and platelet aggregation. Prednisolone also affects the promoter of annexin-1, an important inflammatory protein as it affects leukocytes and blocks phospholipase A2 which reduces the amount of arachidonic acid being cleaved from the phospholipid bilayer. Reducing the amount of arachidonic acid formed further decreases concentrations of prostanoids mentioned calming inflammation.
References
Prednisone Anti-inflammatory Pathway References
Kim S. W, Ko J, Kim J. H, Choi E. C, Na D. S. Differential effects of annexins I, II, III, and V on cytosolic phospholipase A2 activity: specific interaction model. FEBS Letters 489: 243-248, 2001.
Schijvens AM, Ter Heine R, de Wildt SN, Schreuder MF: Pharmacology and pharmacogenetics of prednisone and prednisolone in patients with nephrotic syndrome. Pediatr Nephrol. 2019 Mar;34(3):389-403. doi: 10.1007/s00467-018-3929-z. Epub 2018 Mar 16.
Pubmed: 29549463
Necela B. M, Cidlowski J. A. Mechanisms of Glucocorticoid Receptor Action in Noninflammatory and Inflammatory Cells. American Thoracic Society 1:239-246, 2004.
Hess J, Angel P, Schorpp-Kistner M. AP-1 subunits: quarrel and harmony among siblings. Journal of Cell Sciences 117: 5965-5973, 2004.
Lim J. W, Kim H, Kim K. H. Nuclear Factor-kB Regulates Cyclooxygenase-2 Expression and Cell Proliferation in Human Gastric Cancer Cells. Laboratory Investigation 81 (3): 349- 360, 2001.
Kim S, Oh J, No J, Bang Y, Juhnn Y, Song Y. Involvement of NF-kB and AP-1 in COX-2 upregulation by human papillomavirus 16 E5 oncoprotein. Carcinogenesis 30(5): 753-757, 2009.
Perretti M, Dalli J. Exploiting the Annexin A1 pathway for the development of novel anti-inflammatory therapeutics. British Journal of Pharmacology 158: 936-946, 2009.
Oeckinghaus A, Ghosh S. The NF-kB Family of Transcription Factors and Its Regulation. Cold Spring Harb Perspect Biol 1(4): a000034, 2009.
Cartwright T, Perkins N. D, Wilson C. L. NFKB1: a suppressor of inflammation, ageing and cancer. FEBS Journal 283: 1812-1822, 2016.
Caldenhoven E, Liden J, Wissink S, Wan de Stolpe A, Raaijmakers J, Koenderman L, Okret S, Gustafsson J, Van der Saag P, T. Negative Cross-Talk between ReAl and the Glucocorticoid Receptor: A Possible Mechanism for the Anti-inflammatory Action of Glucocorticoids. Molecular Endocrinology 9(4): 401-412, 1995.
Kang Y, Mbonye U. R, DeLong C. J, Wada M, Smith W. L. Regulation of Intracellular Cyclooxygenase Levels by Gene Transcription and Protein Degradation. Prog Lipid Res 46(2): 108-125, 2007.
Savinova O. V, Hoffmann A, Ghosh G. The Nfkb1 and Nfkb2 Proteins p105 and p100 Function as the Core of High-Molecular-Weight Heterogeneous Complexes. Mol Cell 34(5): 591-602, 2009.
Kirschke E, Goswami D, Southworth D, Griffin P. R, Agard D. Glucocorticoid Receptor Function Regulated by Coordinated Action of the Hsp90 and Hsp70 Chaperone Cycles. Cell 157(7): 1685-1697, 2014.
Perretti M, D’Acquisto F. Annexin A1 and glucocorticoids as effectors of the resolution of inflammation. Nature Reviews Immunology 9: 62–70, 2009.
Parente L, Solito E. Annexin 1: more than an anti-phospholipase protein. Inflammation Research 53: 125-132, 2004.
Fernandes S, McKay G. Prednisolone. Practical Diabetes 30(4): 251-252, 2013.
Rosenson R. S, Gelb M. H. Secretory Phospholipase A2: A Multifaceted Family of Proatherogenic Enzymes. Current Cardiology Reports 11: 445-451, 2009.
Liu T, Zhang L, Joo D, Sun S. NF-κB signaling in inflammation. Signal Transduction and Targeted Therapy 2: 17023, 2017.
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
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