Skip to main content
SpringerLink
Log in
Book cover

Systemic Corticosteroids for Inflammatory Disorders in Pediatrics pp 105–121Cite as

Glucocorticoids in Pediatric Gastrointestinal Disorders

  • Chapter

  • 768 Accesses

Abstract

Pediatric-onset inflammatory bowel disease (IBD) is becoming more common and represents the most frequent chronic intestinal disorder in children. Childhood IBD is generally more extended, more severe, and progresses more rapidly than its adult counterpart. Despite the introduction of highly effective biological agents, glucocorticoids (GCs) are still used to induce remission in moderate to severe IBD, but considerable interindividual differences in their efficacy and several side effects have been reported. In recent years, detailed knowledge of the GC mechanism of action and of the genetic variants affecting GC activity at the molecular level has been gained from several studies: Polymorphisms in genes involved in the GC mechanisms of action, transport, and/or metabolism have been suggested as possible candidates that could play a role in the interindividual differences in the efficacy and toxicity that have been observed. More recent emerging data have implicated the deregulated expression of certain microRNA (miRNA) networks in the pathogenesis of autoimmune and inflammatory diseases, including IBD. miRNAs are small, noncoding RNA molecules that suppress gene expression at the posttranscriptional level, and there is great interest in identifying the role of miRNAs in the modulation of pharmacological response, such as the GC response in patients with IBD.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Baldassano RN, Piccoli DA (1999) Inflammatory bowel disease in pediatric and adolescent patients. Gastroenterol Clin North Am 28(2):445–458

    CAS  PubMed  Google Scholar 

  2. Hyams JS (1996) Crohn’s disease in children. Pediatr Clin North Am 43(1):255–277

    CAS  PubMed  Google Scholar 

  3. Michail S, Ramsy M, Soliman E (2012) Advances in inflammatory bowel diseases in children. Minerva Pediatr 64(3):257–270

    CAS  PubMed  Google Scholar 

  4. Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 126(6):1504–1517

    PubMed  Google Scholar 

  5. Longobardi T, Jacobs P, Bernstein CN (2004) Utilization of health care resources by individuals with inflammatory bowel disease in the United States: a profile of time since diagnosis. Am J Gastroenterol 99(4):650–655

    PubMed  Google Scholar 

  6. Carter MJ, Lobo AJ, Travis SP (2004) Guidelines for the management of inflammatory bowel disease in adults. Gut 53(Suppl 5):V1–V16

    PubMed Central  PubMed  Google Scholar 

  7. Ross SC, Strachan J, Russell RK, Wilson SL (2011) Psychosocial functioning and health-related quality of life in paediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 53(5):480–488

    PubMed  Google Scholar 

  8. Dretzke J, Edlin R, Round J, Connock M, Hulme C, Czeczot J, Fry-Smith A, McCabe C, Meads C (2011) A systematic review and economic evaluation of the use of tumour necrosis factor-alpha (TNF-alpha) inhibitors, adalimumab and infliximab, for Crohn’s disease. Health Technol Assess (Winchester, England) 15(6):1–244

    CAS  Google Scholar 

  9. Friedman S (2004) General principles of medical therapy of inflammatory bowel disease. Gastroenterol Clin North Am 33(2):191–208, viii

    PubMed  Google Scholar 

  10. Faubion WA Jr, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Sandborn WJ (2001) The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology 121(2):255–260

    CAS  PubMed  Google Scholar 

  11. Kansal S, Wagner J, Kirkwood CD, Catto-Smith AG (2013) Enteral nutrition in Crohn’s disease: an underused therapy. Gastroenterol Res Pract 2013:482108

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Markowitz J, Grancher K, Kohn N, Lesser M, Daum F (2000) A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn’s disease. Gastroenterology 119(4):895–902

    CAS  PubMed  Google Scholar 

  13. Hyams J, Markowitz J, Lerer T, Griffiths A, Mack D, Bousvaros A, Otley A, Evans J, Pfefferkorn M, Rosh J, Rothbaum R, Kugathasan S, Mezoff A, Wyllie R, Tolia V, delRosario JF, Moyer MS, Oliva-Hemker M, Leleiko N (2006) The natural history of corticosteroid therapy for ulcerative colitis in children. Clin Gastroenterol Hepatol 4(9):1118–1123

    CAS  PubMed  Google Scholar 

  14. Markowitz J, Hyams J, Mack D, Leleiko N, Evans J, Kugathasan S, Pfefferkorn M, Mezoff A, Rosh J, Tolia V, Otley A, Griffiths A, Moyer MS, Oliva-Hemker M, Wyllie R, Rothbaum R, Bousvaros A, Del Rosario JF, Hale S, Lerer T (2006) Corticosteroid therapy in the age of infliximab: acute and 1-year outcomes in newly diagnosed children with Crohn’s disease. Clin Gastroenterol Hepatol 4(9):1124–1129

    CAS  PubMed  Google Scholar 

  15. Ruemmele FM, Veres G, Kolho KL, Griffiths A, Levine A, Escher JC, Amil Dias J, Barabino A, Braegger CP, Bronsky J, Buderus S, Martin-de-Carpi J, De Ridder L, Fagerberg UL, Hugot JP, Kierkus J, Kolacek S, Koletzko S, Lionetti P, Miele E, Navas Lopez VM, Paerregaard A, Russell RK, Serban DE, Shaoul R, Van Rheenen P, Veereman G, Weiss B, Wilson D, Dignass A, Eliakim A, Winter H, Turner D (2014) Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis 8(10):1179–1207

    PubMed  Google Scholar 

  16. Carvalho R, Hyams JS (2007) Diagnosis and management of inflammatory bowel disease in children. Semin Pediatr Surg 16(3):164–171

    PubMed  Google Scholar 

  17. Thomsen OO, Cortot A, Jewell D, Wright JP, Winter T, Veloso FT, Vatn M, Persson T, Pettersson E (1998) A comparison of budesonide and mesalamine for active Crohn’s disease. International Budesonide-Mesalamine Study Group. N Engl J Med 339(6):370–374

    CAS  PubMed  Google Scholar 

  18. Wong SC, Macrae VE, McGrogan P, Ahmed SF (2006) The role of pro-inflammatory cytokines in inflammatory bowel disease growth retardation. J Pediatr Gastroenterol Nutr 43(2):144–155

    CAS  PubMed  Google Scholar 

  19. Ballinger AB, Savage MO, Sanderson IR (2003) Delayed puberty associated with inflammatory bowel disease. Pediatr Res 53(2):205–210

    PubMed  Google Scholar 

  20. Ezri J, Marques-Vidal P, Nydegger A (2012) Impact of disease and treatments on growth and puberty of pediatric patients with inflammatory bowel disease. Digestion 85(4):308–319

    CAS  PubMed  Google Scholar 

  21. Wong SC, Catto-Smith AG, Zacharin M (2013) Pathological fractures in paediatric patients with inflammatory bowel disease. Eur J Pediatr 173(2):141–151

    PubMed  Google Scholar 

  22. Vihinen MK, Kolho KL, Ashorn M, Verkasalo M, Raivio T (2008) Bone turnover and metabolism in paediatric patients with inflammatory bowel disease treated with systemic glucocorticoids. Eur J Endocrinol (European Federation of Endocrine Societies) 159(6):693–698

    CAS  Google Scholar 

  23. Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102(2):274–282

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Semeao EJ, Stallings VA, Peck SN, Piccoli DA (1997) Vertebral compression fractures in pediatric patients with Crohn’s disease. Gastroenterology 112(5):1710–1713

    CAS  PubMed  Google Scholar 

  25. Sidoroff M, Kolho KL (2014) Screening for adrenal suppression in children with inflammatory bowel disease discontinuing glucocorticoid therapy. BMC Gastroenterol 14:51

    PubMed Central  PubMed  Google Scholar 

  26. Desrame J, Sabate JM, Agher R, Bremont C, Gaudric M, Couturier D, Chaussade S (2002) Assessment of hypothalamic-pituitary-adrenal axis function after corticosteroid therapy in inflammatory bowel disease. Am J Gastroenterol 97(7):1785–1791

    CAS  PubMed  Google Scholar 

  27. De Iudicibus S, Franca R, Martelossi S, Ventura A, Decorti G (2011) Molecular mechanism of glucocorticoid resistance in inflammatory bowel disease. World J Gastroenterol 17(9):1095–1108

    PubMed Central  PubMed  Google Scholar 

  28. Charmandari E, Kino T (2010) Chrousos syndrome: a seminal report, a phylogenetic enigma and the clinical implications of glucocorticoid signalling changes. Eur J Clin Invest 40(10):932–942. doi:10.1111/j.1365-2362.2010.02336.x

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Charmandari E, Kino T, Chrousos GP (2013) Primary generalized familial and sporadic glucocorticoid resistance (Chrousos syndrome) and hypersensitivity. Endocr Dev 24:67–85

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Beato M, Herrlich P, Schutz G (1995) Steroid hormone receptors: many actors in search of a plot. Cell 83(6):851–857

    CAS  PubMed  Google Scholar 

  31. Davies P, Rushmere NK (1988) The structure and function of steroid receptors. Sci Prog 72(288 Pt 4):563–578

    CAS  PubMed  Google Scholar 

  32. Theriault A, Boyd E, Harrap SB, Hollenberg SM, Connor JM (1989) Regional chromosomal assignment of the human glucocorticoid receptor gene to 5q31. Hum Genet 83(3):289–291

    CAS  PubMed  Google Scholar 

  33. Baker AC, Green TL, Chew VW, Tung K, Amini A, Lim D, Cho K, Greenhalgh DG (2012) Enhanced steroid response of a human glucocorticoid receptor splice variant. Shock 38(1):11–17. doi:10.1097/SHK.0b013e318257c0c0

    CAS  PubMed  Google Scholar 

  34. Lu NZ, Cidlowski JA (2004) The origin and functions of multiple human glucocorticoid receptor isoforms. Ann N Y Acad Sci 1024:102–123. doi:10.1196/annals.1321.008

    CAS  PubMed  Google Scholar 

  35. Revollo JR, Cidlowski JA (2009) Mechanisms generating diversity in glucocorticoid receptor signaling. Ann N Y Acad Sci 1179:167–178. doi:10.1111/j.1749-6632.2009.04986.x

    CAS  PubMed  Google Scholar 

  36. Zhou J, Cidlowski JA (2005) The human glucocorticoid receptor: one gene, multiple proteins and diverse responses. Steroids 70(5–7):407–417. doi:10.1016/j.steroids.2005.02.006

    CAS  PubMed  Google Scholar 

  37. Oakley RH, Sar M, Cidlowski JA (1996) The human glucocorticoid receptor beta isoform. Expression, biochemical properties, and putative function. J Biol Chem 271(16):9550–9559

    CAS  PubMed  Google Scholar 

  38. Wu I, Shin SC, Cao Y, Bender IK, Jafari N, Feng G, Lin S, Cidlowski JA, Schleimer RP, Lu NZ (2013) Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes. Cell Death Dis 4:e453. doi:10.1038/cddis.2012.193

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Lu NZ, Cidlowski JA (2005) Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol Cell 18(3):331–342. doi:10.1016/j.molcel.2005.03.025

    CAS  PubMed  Google Scholar 

  40. Hutchison KA, Scherrer LC, Czar MJ, Ning Y, Sanchez ER, Leach KL, Deibel MR Jr, Pratt WB (1993) FK506 binding to the 56-kilodalton immunophilin (Hsp56) in the glucocorticoid receptor heterocomplex has no effect on receptor folding or function. Biochemistry 32(15):3953–3957

    CAS  PubMed  Google Scholar 

  41. Pratt WB, Morishima Y, Murphy M, Harrell M (2006) Chaperoning of glucocorticoid receptors. Handb Exp Pharmacol 172:111–138

    CAS  PubMed  Google Scholar 

  42. Gross KL, Lu NZ, Cidlowski JA (2009) Molecular mechanisms regulating glucocorticoid sensitivity and resistance. Mol Cell Endocrinol 300(1–2):7–16. doi:10.1016/j.mce.2008.10.001

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Wikstrom AC (2003) Glucocorticoid action and novel mechanisms of steroid resistance: role of glucocorticoid receptor-interacting proteins for glucocorticoid responsiveness. J Endocrinol 178(3):331–337

    PubMed  Google Scholar 

  44. Qian X, Zhu Y, Xu W, Lin Y (2001) Glucocorticoid receptor and heat shock protein 90 in peripheral blood mononuclear cells from asthmatics. Chin Med J (Engl) 114(10):1051–1054

    CAS  Google Scholar 

  45. Raddatz D, Middel P, Bockemuhl M, Benohr P, Wissmann C, Schworer H, Ramadori G (2004) Glucocorticoid receptor expression in inflammatory bowel disease: evidence for a mucosal down-regulation in steroid-unresponsive ulcerative colitis. Aliment Pharmacol Ther 19(1):47–61

    CAS  PubMed  Google Scholar 

  46. Matysiak M, Makosa B, Walczak A, Selmaj K (2008) Patients with multiple sclerosis resisted to glucocorticoid therapy: abnormal expression of heat-shock protein 90 in glucocorticoid receptor complex. Mult Scler 14(7):919–926. doi:10.1177/1352458508090666

    CAS  PubMed  Google Scholar 

  47. Damjanovic SS, Antic JA, Ilic BB, Cokic BB, Ivovic M, Ognjanovic SI, Isailovic TV, Popovic BM, Bozic IB, Tatic S, Matic G, Todorovic VN, Paunovic I (2012) Glucocorticoid receptor and molecular chaperones in the pathogenesis of adrenal incidentalomas: potential role of reduced sensitivity to glucocorticoids. Mol Med 18:1456–1465. doi:10.2119/molmed.2012.00261

    CAS  PubMed Central  Google Scholar 

  48. Ouyang J, Chen P, Jiang T, Chen Y, Li J (2012) Nuclear HSP90 regulates the glucocorticoid responsiveness of PBMCs in patients with idiopathic nephrotic syndrome. Int Immunopharmacol 14(3):334–340. doi:10.1016/j.intimp.2012.08.012

    CAS  PubMed  Google Scholar 

  49. Pemberton LF, Paschal BM (2005) Mechanisms of receptor-mediated nuclear import and nuclear export. Traffic 6(3):187–198. doi:10.1111/j.1600-0854.2005.00270.x

    CAS  PubMed  Google Scholar 

  50. Almawi WY, Melemedjian OK (2002) Molecular mechanisms of glucocorticoid antiproliferative effects: antagonism of transcription factor activity by glucocorticoid receptor. J Leukoc Biol 71(1):9–15

    CAS  PubMed  Google Scholar 

  51. Meijsing SH, Pufall MA, So AY, Bates DL, Chen L, Yamamoto KR (2009) DNA binding site sequence directs glucocorticoid receptor structure and activity. Science 324(5925):407–410. doi:10.1126/science.1164265

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Nordeen SK, Suh BJ, Kuhnel B, Hutchison CA 3rd (1990) Structural determinants of a glucocorticoid receptor recognition element. Mol Endocrinol 4(12):1866–1873

    CAS  PubMed  Google Scholar 

  53. De Bosscher K, Vanden Berghe W, Vermeulen L, Plaisance S, Boone E, Haegeman G (2000) Glucocorticoids repress NF-kappaB-driven genes by disturbing the interaction of p65 with the basal transcription machinery, irrespective of coactivator levels in the cell. Proc Natl Acad Sci U S A 97(8):3919–3924

    PubMed Central  PubMed  Google Scholar 

  54. Schacke H, Docke WD, Asadullah K (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96(1):23–43

    CAS  PubMed  Google Scholar 

  55. Schacke H, Schottelius A, Docke WD, Strehlke P, Jaroch S, Schmees N, Rehwinkel H, Hennekes H, Asadullah K (2004) Dissociation of transactivation from transrepression by a selective glucocorticoid receptor agonist leads to separation of therapeutic effects from side effects. Proc Natl Acad Sci U S A 101(1):227–232. doi:10.1073/pnas.0300372101

    PubMed Central  PubMed  Google Scholar 

  56. Song IH, Gold R, Straub RH, Burmester GR, Buttgereit F (2005) New glucocorticoids on the horizon: repress, don’t activate! J Rheumatol 32(7):1199–1207

    CAS  Google Scholar 

  57. Chen R, Burke TF, Cumberland JE, Brummet M, Beck LA, Casolaro V, Georas SN (2000) Glucocorticoids inhibit calcium- and calcineurin-dependent activation of the human IL-4 promoter. J Immunol 164(2):825–832

    CAS  PubMed  Google Scholar 

  58. Yang-Yen HF, Chambard JC, Sun YL, Smeal T, Schmidt TJ, Drouin J, Karin M (1990) Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell 62(6):1205–1215

    CAS  PubMed  Google Scholar 

  59. Ray A, Prefontaine KE (1994) Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Proc Natl Acad Sci U S A 91(2):752–756

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Stocklin E, Wissler M, Gouilleux F, Groner B (1996) Functional interactions between Stat5 and the glucocorticoid receptor. Nature 383(6602):726–728. doi:10.1038/383726a0

    CAS  PubMed  Google Scholar 

  61. Ing NH (2005) Steroid hormones regulate gene expression posttranscriptionally by altering the stabilities of messenger RNAs. Biol Reprod 72(6):1290–1296. doi:10.1095/biolreprod.105.040014

    CAS  PubMed  Google Scholar 

  62. Croxtall JD, van Hal PT, Choudhury Q, Gilroy DW, Flower RJ (2002) Different glucocorticoids vary in their genomic and non-genomic mechanism of action in A549 cells. Br J Pharmacol 135(2):511–519. doi:10.1038/sj.bjp.0704474

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Croxtall JD, Flower RJ (1992) Lipocortin 1 mediates dexamethasone-induced growth arrest of the A549 lung adenocarcinoma cell line. Proc Natl Acad Sci U S A 89(8):3571–3575

    CAS  PubMed Central  PubMed  Google Scholar 

  64. McConkey DJ, Nicotera P, Hartzell P, Bellomo G, Wyllie AH, Orrenius S (1989) Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration. Arch Biochem Biophys 269(1):365–370. doi:10.1016/0003-9861(89)90119-7

    CAS  PubMed  Google Scholar 

  65. Cohen JJ, Duke RC (1984) Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol 132(1):38–42

    CAS  PubMed  Google Scholar 

  66. Ho GT, Chiam P, Drummond H, Loane J, Arnott ID, Satsangi J (2006) The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5-year UK inception cohort. Aliment Pharmacol Ther 24(2):319–330

    CAS  PubMed  Google Scholar 

  67. Hyams JS, Lerer T, Griffiths A, Pfefferkorn M, Kugathasan S, Evans J, Otley A, Carvalho R, Mack D, Bousvaros A, Rosh J, Mamula P, Kay M, Crandall W, Oliva-Hemker M, Keljo D, LeLeiko N, Markowitz J (2009) Long-term outcome of maintenance infliximab therapy in children with Crohn’s disease. Inflamm Bowel Dis 15(6):816–822

    PubMed  Google Scholar 

  68. van Rossum EF, Lamberts SW (2004) Polymorphisms in the glucocorticoid receptor gene and their associations with metabolic parameters and body composition. Recent Prog Horm Res 59:333–357

    PubMed  Google Scholar 

  69. van Rossum EF, Koper JW, Huizenga NA, Uitterlinden AG, Janssen JA, Brinkmann AO, Grobbee DE, de Jong FH, van Duyn CM, Pols HA, Lamberts SW (2002) A polymorphism in the glucocorticoid receptor gene, which decreases sensitivity to glucocorticoids in vivo, is associated with low insulin and cholesterol levels. Diabetes 51(10):3128–3134

    PubMed  Google Scholar 

  70. Manenschijn L, van den Akker EL, Lamberts SW, van Rossum EF (2009) Clinical features associated with glucocorticoid receptor polymorphisms. An overview. Ann N Y Acad Sci 1179:179–198

    CAS  PubMed  Google Scholar 

  71. Detera-Wadleigh SD, Encio IJ, Rollins DY, Coffman D, Wiesch D (1991) A TthIII1 polymorphism on the 5′ flanking region of the glucocorticoid receptor gene (GRL). Nucleic Acids Res 19(8):1960. doi:10.1093/nar/19.8.1960-a

    CAS  PubMed Central  PubMed  Google Scholar 

  72. van Rossum EF, Roks PH, de Jong FH, Brinkmann AO, Pols HA, Koper JW, Lamberts SW (2004) Characterization of a promoter polymorphism in the glucocorticoid receptor gene and its relationship to three other polymorphisms. Clin Endocrinol (Oxf) 61(5):573–581

    Google Scholar 

  73. de Lange P, Koper JW, Huizenga NA, Brinkmann AO, de Jong FH, Karl M, Chrousos GP, Lamberts SW (1997) Differential hormone-dependent transcriptional activation and -repression by naturally occurring human glucocorticoid receptor variants. Mol Endocrinol (Baltimore, MD) 11(8):1156–1164

    Google Scholar 

  74. De Iudicibus S, Stocco G, Martelossi S, Drigo I, Norbedo S, Lionetti P, Pozzi E, Barabino A, Decorti G, Bartoli F, Ventura A (2007) Association of BclI polymorphism of the glucocorticoid receptor gene locus with response to glucocorticoids in inflammatory bowel disease. Gut 56(9):1319–1320

    PubMed Central  PubMed  Google Scholar 

  75. Maltese P, Palma L, Sfara C, de Rocco P, Latiano A, Palmieri O, Corritore G, Annese V, Magnani M (2012) Glucocorticoid resistance in Crohn’s disease and ulcerative colitis: an association study investigating GR and FKBP5 gene polymorphisms. Pharmacogenomics J 12(5):432–438

    CAS  PubMed  Google Scholar 

  76. Koper JW, van Rossum EF, van den Akker EL (2014) Glucocorticoid receptor polymorphisms and haplotypes and their expression in health and disease. Steroids 92C:62–73

    Google Scholar 

  77. Schaaf MJ, Cidlowski JA (2002) AUUUA motifs in the 3′UTR of human glucocorticoid receptor alpha and beta mRNA destabilize mRNA and decrease receptor protein expression. Steroids 67(7):627–636

    CAS  PubMed  Google Scholar 

  78. Hagendorf A, Koper JW, de Jong FH, Brinkmann AO, Lamberts SW, Feelders RA (2005) Expression of the human glucocorticoid receptor splice variants alpha, beta, and P in peripheral blood mononuclear leukocytes in healthy controls and in patients with hyper- and hypocortisolism. J Clin Endocrinol Metab 90(11):6237–6243

    CAS  PubMed  Google Scholar 

  79. Lewis-Tuffin LJ, Cidlowski JA (2006) The physiology of human glucocorticoid receptor beta (hGRbeta) and glucocorticoid resistance. Ann N Y Acad Sci 1069:1–9

    CAS  PubMed  Google Scholar 

  80. Charmandari E, Chrousos GP, Ichijo T, Bhattacharyya N, Vottero A, Souvatzoglou E, Kino T (2005) The human glucocorticoid receptor (hGR) beta isoform suppresses the transcriptional activity of hGRalpha by interfering with formation of active coactivator complexes. Mol Endocrinol (Baltimore, MD) 19(1):52–64

    CAS  Google Scholar 

  81. Honda M, Orii F, Ayabe T, Imai S, Ashida T, Obara T, Kohgo Y (2000) Expression of glucocorticoid receptor beta in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis. Gastroenterology 118(5):859–866. doi:10.1016/S0016-5085(00)70172-7

    CAS  PubMed  Google Scholar 

  82. Fujishima S, Takeda H, Kawata S, Yamakawa M (2009) The relationship between the expression of the glucocorticoid receptor in biopsied colonic mucosa and the glucocorticoid responsiveness of ulcerative colitis patients. Clin Immunol (Orlando, FL) 133(2):208–217

    CAS  Google Scholar 

  83. van Winsen LL, Hooper-van Veen T, van Rossum EF, Polman CH, van den Berg TK, Koper JW, Uitdehaag BM (2005) The impact of glucocorticoid receptor gene polymorphisms on glucocorticoid sensitivity is outweighted in patients with multiple sclerosis. J Neuroimmunol 167(1–2):150–156

    PubMed  Google Scholar 

  84. Szabo V, Borgulya G, Filkorn T, Majnik J, Banyasz I, Nagy ZZ (2007) The variant N363S of glucocorticoid receptor in steroid-induced ocular hypertension in Hungarian patients treated with photorefractive keratectomy. Mol Vis 13:659–666

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Bonifati DM, Witchel SF, Ermani M, Hoffman EP, Angelini C, Pegoraro E (2006) The glucocorticoid receptor N363S polymorphism and steroid response in Duchenne dystrophy. J Neurol Neurosurg Psychiatry 77(10):1177–1179. doi:10.1136/jnnp.2005.078345

    CAS  PubMed Central  PubMed  Google Scholar 

  86. van Rossum EF, Koper JW, van den Beld AW, Uitterlinden AG, Arp P, Ester W, Janssen JA, Brinkmann AO, de Jong FH, Grobbee DE, Pols HA, Lamberts SW (2003) Identification of the BclI polymorphism in the glucocorticoid receptor gene: association with sensitivity to glucocorticoids in vivo and body mass index. Clin Endocrinol (Oxf) 59(5):585–592

    Google Scholar 

  87. Di Blasio AM, van Rossum EF, Maestrini S, Berselli ME, Tagliaferri M, Podesta F, Koper JW, Liuzzi A, Lamberts SW (2003) The relation between two polymorphisms in the glucocorticoid receptor gene and body mass index, blood pressure and cholesterol in obese patients. Clin Endocrinol (Oxf) 59(1):68–74

    Google Scholar 

  88. De Iudicibus S, Stocco G, Martelossi S, Londero M, Ebner E, Pontillo A, Lionetti P, Barabino A, Bartoli F, Ventura A, Decorti G (2010) Genetic predictors of glucocorticoid response in pediatric patients with inflammatory bowel diseases. J Clin Gastroenterol 45(1):e1–e7. doi:10.1097/MCG.0b013e3181e8ae93

  89. Lane SJ, Adcock IM, Richards D, Hawrylowicz C, Barnes PJ, Lee TH (1998) Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes. J Clin Invest 102(12):2156–2164

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Guo H, Ingolia NT, Weissman JS, Bartel DP (2010) Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 466(7308):835–840. doi:10.1038/nature09267

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Rigoutsos I (2009) New tricks for animal microRNAS: targeting of amino acid coding regions at conserved and nonconserved sites. Cancer Res 69(8):3245–3248. doi:10.1158/0008-5472.CAN-09-0352

    CAS  PubMed  Google Scholar 

  92. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    CAS  PubMed  Google Scholar 

  93. Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP, Burge CB (2003) Prediction of mammalian microRNA targets. Cell 115(7):787–798

    CAS  PubMed  Google Scholar 

  94. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120(1):15–20. doi:10.1016/j.cell.2004.12.035

    CAS  PubMed  Google Scholar 

  95. Friedman Y, Balaga O, Linial M (2013) Working together: combinatorial regulation by microRNAs. Adv Exp Med Biol 774:317–337. doi:10.1007/978-94-007-5590-1_16

    CAS  PubMed  Google Scholar 

  96. Singh TR, Gupta A, Suravajhala P (2013) Challenges in the miRNA research. Int J Bioinform Res Appl 9(6):576–583. doi:10.1504/IJBRA.2013.056620

    CAS  PubMed  Google Scholar 

  97. Iborra M, Bernuzzi F, Invernizzi P, Danese S (2012) MicroRNAs in autoimmunity and inflammatory bowel disease: crucial regulators in immune response. Autoimmun Rev 11(5):305–314

    CAS  PubMed  Google Scholar 

  98. Archanioti P, Gazouli M, Theodoropoulos G, Vaiopoulou A, Nikiteas N (2011) Micro-RNAs as regulators and possible diagnostic bio-markers in inflammatory bowel disease. J Crohns Colitis 5(6):520–524. doi:10.1016/j.crohns.2011.05.007

    PubMed  Google Scholar 

  99. Coskun M, Bjerrum JT, Seidelin JB, Nielsen OH (2012) MicroRNAs in inflammatory bowel disease–pathogenesis, diagnostics and therapeutics. World J Gastroenterol 18(34):4629–4634. doi:10.3748/wjg.v18.i34.4629

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Dalal SR, Kwon JH (2010) The role of microRNA in inflammatory bowel disease. Gastroenterol Hepatol (N Y) 6(11):714–722

    Google Scholar 

  101. Wu F, Zhang S, Dassopoulos T, Harris ML, Bayless TM, Meltzer SJ, Brant SR, Kwon JH (2010) Identification of microRNAs associated with ileal and colonic Crohn’s disease. Inflamm Bowel Dis 16(10):1729–1738

    PubMed Central  PubMed  Google Scholar 

  102. Zahm AM, Thayu M, Hand NJ, Horner A, Leonard MB, Friedman JR (2011) Circulating microRNA is a biomarker of pediatric Crohn disease. J Pediatr Gastroenterol Nutr 53(1):26–33

    CAS  PubMed  Google Scholar 

  103. Wu F, Guo NJ, Tian H, Marohn M, Gearhart S, Bayless TM, Brant SR, Kwon JH (2011) Peripheral blood microRNAs distinguish active ulcerative colitis and Crohn’s disease. Inflamm Bowel Dis 17(1):241–250

    PubMed Central  PubMed  Google Scholar 

  104. Paraskevi A, Theodoropoulos G, Papaconstantinou I, Mantzaris G, Nikiteas N, Gazouli M (2012) Circulating microRNA in inflammatory bowel disease. J Crohns Colitis 6(9):900–904

    PubMed  Google Scholar 

  105. Pekow JR, Kwon JH (2012) MicroRNAs in inflammatory bowel disease. Inflamm Bowel Dis 18(1):187–193

    PubMed Central  PubMed  Google Scholar 

  106. Kertesz M, Iovino N, Unnerstall U, Gaul U, Segal E (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39(10):1278–1284. doi:10.1038/ng2135

    CAS  PubMed  Google Scholar 

  107. Vreugdenhil E, Verissimo CS, Mariman R, Kamphorst JT, Barbosa JS, Zweers T, Champagne DL, Schouten T, Meijer OC, de Kloet ER, Fitzsimons CP (2009) MicroRNA 18 and 124a down-regulate the glucocorticoid receptor: implications for glucocorticoid responsiveness in the brain. Endocrinology 150(5):2220–2228. doi:10.1210/en.2008-1335

    CAS  PubMed  Google Scholar 

  108. Ledderose C, Mohnle P, Limbeck E, Schutz S, Weis F, Rink J, Briegel J, Kreth S (2012) Corticosteroid resistance in sepsis is influenced by microRNA-124–induced downregulation of glucocorticoid receptor-alpha. Crit Care Med 40(10):2745–2753. doi:10.1097/CCM.0b013e31825b8ebc

    CAS  PubMed  Google Scholar 

  109. Tessel MA, Benham AL, Krett NL, Rosen ST, Gunaratne PH (2011) Role for microRNAs in regulating glucocorticoid response and resistance in multiple myeloma. Horm Cancer 2(3):182–189. doi:10.1007/s12672-011-0072-8

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, 34137, Italy

    Sara De Iudicibus & Stefano Martelossi

  2. Department of Life Sciences, University of Trieste, Trieste, 34127, Italy

    Giuliana Decorti

Authors
  1. Sara De Iudicibus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stefano Martelossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuliana Decorti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sara De Iudicibus .

Editor information

Editors and Affiliations

  1. AOU Meyer Pediatric Rheumatology, Firenze, Italy

    Rolando Cimaz

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

De Iudicibus, S., Martelossi, S., Decorti, G. (2015). Glucocorticoids in Pediatric Gastrointestinal Disorders. In: Cimaz, R. (eds) Systemic Corticosteroids for Inflammatory Disorders in Pediatrics. Adis, Cham. https://doi.org/10.1007/978-3-319-16056-6_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-16056-6_9

  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-16055-9

  • Online ISBN: 978-3-319-16056-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation