Glucocorticoid Efficacy in Asthma: is Improved Tissue Remodeling Upstream of Anti-inflammation

Overview

Journal J Investig Med

Publisher Sage Publications

Specialty General Medicine

Date 2009 Sep 5

PMID 19730133

Citations 13

Authors

Robert J Freishtat

Kanneboyina Nagaraju

William Jusko

Eric P Hoffman

Affiliations

Soon will be listed here.

Abstract

Synthetic glucocorticoids (GCs), such as prednisone, are among the most widely prescribed drugs worldwide and are used to treat many acute and chronic inflammatory conditions. The current paradigm of GC efficacy is that they are potent anti-inflammatory agents. Decreased inflammation in many disorders is thought to lead to decreased pathological tissue remodeling. However, this model has never been validated. In particular, improvements in inflammation have not been shown to improve the rate of lung function decline in asthma. Herein, we present an alternative paradigm, where GC efficacy is mediated through more successful tissue remodeling, with reduction in inflammation secondary to successful regeneration.

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References

Almon R, DuBois D, Jusko W . A microarray analysis of the temporal response of liver to methylprednisolone: a comparative analysis of two dosing regimens. Endocrinology. 2007; 148(5):2209-25. PMC: 4183266. DOI: 10.1210/en.2006-0790. View

Fahy J, Corry D, Boushey H . Airway inflammation and remodeling in asthma. Curr Opin Pulm Med. 1999; 6(1):15-20. DOI: 10.1097/00063198-200001000-00004. View

Larj M, Bleecker E . Therapeutic responses in asthma and COPD. Corticosteroids. Chest. 2004; 126(2 Suppl):138S-149S. DOI: 10.1378/chest.126.2_suppl_1.138S. View

Almon R, DuBois D, Yao Z, Hoffman E, Ghimbovschi S, Jusko W . Microarray analysis of the temporal response of skeletal muscle to methylprednisolone: comparative analysis of two dosing regimens. Physiol Genomics. 2007; 30(3):282-99. PMC: 4186702. DOI: 10.1152/physiolgenomics.00242.2006. View

Koyanagi S, Okazawa S, Kuramoto Y, Ushijima K, Shimeno H, Soeda S . Chronic treatment with prednisolone represses the circadian oscillation of clock gene expression in mouse peripheral tissues. Mol Endocrinol. 2005; 20(3):573-83. DOI: 10.1210/me.2005-0165. View

Solito E, Mulla A, Morris J, Christian H, Flower R, Buckingham J . Dexamethasone induces rapid serine-phosphorylation and membrane translocation of annexin 1 in a human folliculostellate cell line via a novel nongenomic mechanism involving the glucocorticoid receptor, protein kinase C, phosphatidylinositol.... Endocrinology. 2003; 144(4):1164-74. DOI: 10.1210/en.2002-220592. View

Weller B, Massa R, Karpati G, Carpenter S . Glucocorticoids and immunosuppressants do not change the prevalence of necrosis and regeneration in mdx skeletal muscles. Muscle Nerve. 1991; 14(8):771-4. DOI: 10.1002/mus.880140812. View

Herrlich P . Cross-talk between glucocorticoid receptor and AP-1. Oncogene. 2001; 20(19):2465-75. DOI: 10.1038/sj.onc.1204388. View

Hida A, Koike N, Hirose M, Hattori M, Sakaki Y, Tei H . The human and mouse Period1 genes: five well-conserved E-boxes additively contribute to the enhancement of mPer1 transcription. Genomics. 2000; 65(3):224-33. DOI: 10.1006/geno.2000.6166. View

10.

Rogers D . Airway goblet cell hyperplasia in asthma: hypersecretory and anti-inflammatory?. Clin Exp Allergy. 2002; 32(8):1124-7. DOI: 10.1046/j.1365-2745.2002.01474.x. View

11.

Dezitter X, Hammoudi F, Belverge N, Deloulme J, Drobecq H, Masselot B . Proteomics unveil corticoid-induced S100A11 shuttling in keratinocyte differentiation. Biochem Biophys Res Commun. 2007; 360(3):627-32. DOI: 10.1016/j.bbrc.2007.06.113. View

12.

Gibbs J, Beesley S, Plumb J, Singh D, Farrow S, Ray D . Circadian timing in the lung; a specific role for bronchiolar epithelial cells. Endocrinology. 2008; 150(1):268-76. PMC: 4340583. DOI: 10.1210/en.2008-0638. View

13.

Burioka N, Takata M, Okano Y, Ohdo S, Fukuoka Y, Miyata M . Dexamethasone influences human clock gene expression in bronchial epithelium and peripheral blood mononuclear cells in vitro. Chronobiol Int. 2005; 22(3):585-90. DOI: 10.1081/CBI-200062416. View

14.

Martinez F . Definition of pediatric asthma and associated risk factors. Pediatr Pulmonol Suppl. 1997; 15:9-12. View

15.

Smolensky M, Lemmer B, Reinberg A . Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma. Adv Drug Deliv Rev. 2007; 59(9-10):852-82. DOI: 10.1016/j.addr.2007.08.016. View

16.

Pelaia G, Vatrella A, Cuda G, Maselli R, Marsico S . Molecular mechanisms of corticosteroid actions in chronic inflammatory airway diseases. Life Sci. 2003; 72(14):1549-61. DOI: 10.1016/s0024-3205(02)02446-3. View

17.

Le Minh N, Damiola F, Tronche F, Schutz G, Schibler U . Glucocorticoid hormones inhibit food-induced phase-shifting of peripheral circadian oscillators. EMBO J. 2001; 20(24):7128-36. PMC: 125339. DOI: 10.1093/emboj/20.24.7128. View

18.

Heitzer M, Wolf I, Sanchez E, Witchel S, DeFranco D . Glucocorticoid receptor physiology. Rev Endocr Metab Disord. 2007; 8(4):321-30. DOI: 10.1007/s11154-007-9059-8. View

19.

Yang X, Ogryzko V, Nishikawa J, Howard B, Nakatani Y . A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 1996; 382(6589):319-24. DOI: 10.1038/382319a0. View

20.

Shearman L, Sriram S, Weaver D, Maywood E, Chaves I, Zheng B . Interacting molecular loops in the mammalian circadian clock. Science. 2000; 288(5468):1013-9. DOI: 10.1126/science.288.5468.1013. View