Skip to main content
SpringerLink
Log in

Potential Role of Mast Cells in Regulating Corticosteroid Insensitivity in Severe Asthma

  • Chapter
  • First Online:
Lung Inflammation in Health and Disease, Volume I

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1303))

Abstract

The mechanisms driving corticosteroid insensitivity in asthma are still unclear although evidence points toward a potential role of lung mast cells. Indeed, a number of in vitro studies using various cell types showed that different mediators produced by activated mast cells, including cytokines, have the capacity to interfere with the therapeutic action of corticosteroids. In patients with severe allergic refractory asthma, the anti-IgE monoclonal antibody (mAb), Omalizumab, has been shown to be associated with a marked reduction in inhaled and systemic use of corticosteroids, further suggesting a key role of mast cells in the poor response of patients to these drugs. The present chapter will discuss the possible underlying mechanisms by which mast cells could contribute to reducing corticosteroid sensitivity seen in patients with severe asthma.

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

Access this chapter

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 229.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
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

Institutional subscriptions

References

  1. Holgate ST. Innate and adaptive immune responses in asthma. Nat Med. 2012;18:673.

    Article  PubMed  CAS  Google Scholar 

  2. Hinks TS, Zhou X, Staples KJ, Dimitrov BD, Manta A, Petrossian T, Lum PY, Smith CG, Ward JA, Howarth PH, Walls AF, Gadola SD, Djukanovic R. Innate and adaptive T cells in asthmatic patients: relationship to severity and disease mechanisms. J Allergy Clin Immunol. 2015;136:323.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Bradding P, Arthur G. Mast cells in asthma – state of the art. Clin Exp Allergy. 2016;46:194.

    Article  PubMed  CAS  Google Scholar 

  4. Chachi L, Alzahrani A, Koziol-White C, Biddle M, Bagadood R, Panettieri RA Jr, Bradding P, Amrani Y. Increased beta2-adrenoceptor phosphorylation in airway smooth muscle in severe asthma: possible role of mast cell-derived growth factors. Clin Exp Immunol. 2018;194:253.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Lewis RJ, Chachi L, Newby C, Amrani Y, Bradding P. Bidirectional counterregulation of human lung mast cell and airway smooth muscle beta2 adrenoceptors. J Immunol. 2016;196:55.

    Article  PubMed  CAS  Google Scholar 

  6. Amrani Y, Bradding P. beta2-adrenoceptor function in asthma. Adv Immunol. 2017;136:1.

    Article  PubMed  CAS  Google Scholar 

  7. Cruse G, Yang W, Duffy SM, Chachi L, Leyland M, Amrani Y, Bradding P. Counterregulation of beta(2)-adrenoceptor function in human mast cells by stem cell factor. J Allergy Clin Immunol. 2010;125:257.

    Article  PubMed  CAS  Google Scholar 

  8. Pesci A, Foresi A, Bertorelli G, Chetta A, Olivieri D. Histochemical characteristics and degranulation of mast cells in epithelium and lamina propria of bronchial biopsies from asthmatic and normal subjects. Am Rev Respir Dis. 1993;147:684.

    Article  PubMed  CAS  Google Scholar 

  9. Carroll NG, Mutavdzic S, James AL. Increased mast cells and neutrophils in submucosal mucous glands and mucus plugging in patients with asthma. Thorax. 2002a;57:677.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Carroll NG, Mutavdzic S, James AL. Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J. 2002b;19:879.

    Article  PubMed  CAS  Google Scholar 

  11. Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID. Mast-cell infiltration of airway smooth muscle in asthma. N Engl J Med. 2002;346:1699.

    Article  PubMed  Google Scholar 

  12. Berger P, Girodet PO, Begueret H, Ousova O, Perng DW, Marthan R, Walls AF, Tunon de Lara JM. Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis. FASEB J. 2003;17:2139.

    Article  PubMed  CAS  Google Scholar 

  13. Bradding P. Clin Exp Allergy. 1996;26(1):13–9. https://doi.org/10.1111/j.1365-2222.1996.tb00051.x.

  14. Amin K, Janson C, Boman G, Venge P. The extracellular deposition of mast cell products is increased in hypertrophic airways smooth muscles in allergic asthma but not in nonallergic asthma. Allergy. 2005;60:1241.

    Article  PubMed  CAS  Google Scholar 

  15. Brightling CE, Ammit AJ, Kaur D, Black JL, Wardlaw AJ, Hughes JM, Bradding P. The CXCL10/CXCR3 axis mediates human lung mast cell migration to asthmatic airway smooth muscle. Am J Respir Crit Care Med. 2005;171:1103.

    Article  PubMed  Google Scholar 

  16. El-Shazly A, Berger P, Girodet PO, Ousova O, Fayon M, Vernejoux JM, Marthan R, Tunon-de-Lara JM. Fraktalkine produced by airway smooth muscle cells contributes to mast cell recruitment in asthma. J Immunol. 2006;176:1860.

    Article  PubMed  CAS  Google Scholar 

  17. Begueret H, Berger P, Vernejoux JM, Dubuisson L, Marthan R, Tunon-de-Lara JM. Inflammation of bronchial smooth muscle in allergic asthma. Thorax. 2007;62:8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Woodman L, Siddiqui S, Cruse G, Sutcliffe A, Saunders R, Kaur D, Bradding P, Brightling C. Mast cells promote airway smooth muscle cell differentiation via autocrine up-regulation of TGF-beta 1. J Immunol. 2008;181:5001.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Balzar et al. Am J Respir Crit Care Med. 2011;183(3):299–309. https://doi.org/10.1164/rccm.201002-0295OC.

  20. Heaney LG, Robinson DS. Severe asthma treatment: need for characterising patients. Lancet. 2005;365:974.

    Article  PubMed  Google Scholar 

  21. Chung KF. New treatments for severe treatment-resistant asthma: targeting the right patient. Lancet Respir Med. 2013;1:639.

    Article  PubMed  CAS  Google Scholar 

  22. Hoshino M, Ohtawa J. Effects of adding omalizumab, an anti-immunoglobulin E antibody, on airway wall thickening in asthma. Respiration. 2012;83:520.

    Article  PubMed  CAS  Google Scholar 

  23. Lai T, Wang S, Xu Z, Zhang C, Zhao Y, Hu Y, Cao C, Ying S, Chen Z, Li W, Wu B, Shen H. Long-term efficacy and safety of omalizumab in patients with persistent uncontrolled allergic asthma: a systematic review and meta-analysis. Sci Rep. 2015;5:8191.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Lin CH, Cheng SL. A review of omalizumab for the management of severe asthma. Drug Des Devel Ther. 2016;10:2369.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Busse W, Corren J, Lanier BQ, McAlary M, Fowler-Taylor A, Cioppa GD, van As A, Gupta N. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. J Allergy Clin Immunol. 2001;108:184.

    Article  PubMed  CAS  Google Scholar 

  26. Subramaniam A, Al-Alawi M, Hamad S, O’Callaghan J, Lane SJ. A study into efficacy of omalizumab therapy in patients with severe persistent allergic asthma at a tertiary referral centre for asthma in Ireland. QJM. 2013;106:631.

    Article  PubMed  CAS  Google Scholar 

  27. D’Amato G, Stanziola A, Sanduzzi A, Liccardi G, Salzillo A, Vitale C, Molino A, Vatrella A, D’Amato M. Treating severe allergic asthma with anti-IgE monoclonal antibody (omalizumab): a review. Multidiscip Respir Med. 2014;9:23.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Carroll WD, Lenney W, Child F, Strange RC, Jones PW, Whyte MK, Primhak RA, Fryer AA. Asthma severity and atopy: how clear is the relationship? Arch Dis Child. 2006;91:405.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. MacDonald KM, Kavati A, Ortiz B, Alhossan A, Lee CS, Abraham I. Short- and long-term real-world effectiveness of omalizumab in severe allergic asthma: systematic review of 42 studies published 2008-2018. Expert Rev Clin Immunol. 2019;15:553.

    Article  PubMed  CAS  Google Scholar 

  30. Fajt ML, Wenzel SE. Mast cells, their subtypes, and relation to asthma phenotypes. Ann Am Thorac Soc. 2013;10(Suppl):S158.

    Article  PubMed  CAS  Google Scholar 

  31. Martinez FD, Vercelli D. Asthma. Lancet. 2013;382:1360.

    Article  PubMed  Google Scholar 

  32. Wang YH, Wills-Karp M. The potential role of interleukin-17 in severe asthma. Curr Allergy Asthma Rep. 2011;11:388.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Hew M, Bhavsar P, Torrego A, Meah S, Khorasani N, Barnes PJ, Adcock I, Chung KF. Relative corticosteroid insensitivity of peripheral blood mononuclear cells in severe asthma. Am J Respir Crit Care Med. 2006;174:134.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Bhavsar P, Khorasani N, Hew M, Johnson M, Chung KF. Effect of p38 MAPK inhibition on corticosteroid suppression of cytokine release in severe asthma. Eur Respir J. 2010;35:750.

    Article  PubMed  CAS  Google Scholar 

  35. Mercado N, Hakim A, Kobayashi Y, Meah S, Usmani OS, Chung KF, Barnes PJ, Ito K. Restoration of corticosteroid sensitivity by p38 mitogen activated protein kinase inhibition in peripheral blood mononuclear cells from severe asthma. PLoS One. 2012;7:e41582.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Bhavsar P, Hew M, Khorasani N, Torrego A, Barnes PJ, Adcock I, Chung KF. Relative corticosteroid insensitivity of alveolar macrophages in severe asthma compared with non-severe asthma. Thorax. 2008;63:784.

    Article  PubMed  CAS  Google Scholar 

  37. Lea S, Harbron C, Khan N, Booth G, Armstrong J, Singh D. Corticosteroid insensitive alveolar macrophages from asthma patients; synergistic interaction with a p38 mitogen-activated protein kinase (MAPK) inhibitor. Br J Clin Pharmacol. 2015;79:756.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Matthews JG, Ito K, Barnes PJ, Adcock IM. Defective glucocorticoid receptor nuclear translocation and altered histone acetylation patterns in glucocorticoid-resistant patients. J Allergy Clin Immunol. 2004;113:1100.

    Article  PubMed  CAS  Google Scholar 

  39. Goleva E, Jackson LP, Gleason M, Leung DY. Usefulness of PBMCs to predict clinical response to corticosteroids in asthmatic patients. J Allergy Clin Immunol. 2012;129:687.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Wang M, Gao P, Wu X, Chen Y, Feng Y, Yang Q, Xu Y, Zhao J, Xie J. Impaired anti-inflammatory action of glucocorticoid in neutrophil from patients with steroid-resistant asthma. Respir Res. 2016;17:153.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Hershko AY, Suzuki R, Charles N, Alvarez-Errico D, Sargent JL, Laurence A, Rivera J. Mast cell interleukin-2 production contributes to suppression of chronic allergic dermatitis. Immunity. 2011;35:562.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Salamon P, Shefler I, Moshkovits I, Munitz A, Horwitz Klotzman D, Mekori YA, Hershko AY. IL-33 and IgE stimulate mast cell production of IL-2 and regulatory T cell expansion in allergic dermatitis. Clin Exp Allergy. 2017;47:1409.

    Article  PubMed  CAS  Google Scholar 

  43. Kam JC, Szefler SJ, Surs W, Sher ER, Leung DY. Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. J Immunol. 1993;151:3460.

    Article  PubMed  CAS  Google Scholar 

  44. Goleva E, Li LB, Leung DY. IFN-gamma reverses IL-2- and IL-4-mediated T-cell steroid resistance. Am J Respir Cell Mol Biol. 2009;40:223.

    Article  PubMed  CAS  Google Scholar 

  45. Vazquez-Tello A, Halwani R, Hamid Q, Al-Muhsen S. Glucocorticoid receptor-beta up-regulation and steroid resistance induction by IL-17 and IL-23 cytokine stimulation in peripheral mononuclear cells. J Clin Immunol. 2013;33:466.

    Article  PubMed  CAS  Google Scholar 

  46. Pazdrak K, Straub C, Maroto R, Stafford S, White WI, Calhoun WJ, Kurosky A. Cytokine-induced glucocorticoid resistance from eosinophil activation: protein phosphatase 5 modulation of glucocorticoid receptor phosphorylation and signaling. J Immunol. 2016;197:3782.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Kanagalingam T, Solomon L, Vijeyakumaran M, Palikhe NS, Vliagoftis H, Cameron L. IL-2 modulates Th2 cell responses to glucocorticosteroid: a cause of persistent type 2 inflammation? Immun Inflamm Dis. 2019;7:112.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Hart PH. Regulation of the inflammatory response in asthma by mast cell products. Immunol Cell Biol. 2001;79:149.

    Article  PubMed  CAS  Google Scholar 

  49. Brightling C, Berry M, Amrani Y. Targeting TNF-alpha: a novel therapeutic approach for asthma. J Allergy Clin Immunol. 2008;121:5.

    Article  PubMed  CAS  Google Scholar 

  50. Nishimoto Y, Iwamoto I, Suzuki A, Ueda K, Kimura G, Ito K, Kizawa Y. TNF-alpha decreased corticosteroid responsiveness in mice models of airway inflammation induced by double strand RNA and/or tobacco smoke exposure. Yakugaku Zasshi. 2019;139:955.

    Article  PubMed  CAS  Google Scholar 

  51. Dejager L, Dendoncker K, Eggermont M, Souffriau J, Van Hauwermeiren F, Willart M, Van Wonterghem E, Naessens T, Ballegeer M, Vandevyver S, Hammad H, Lambrecht B, De Bosscher K, Grooten J, Libert C. Neutralizing TNFalpha restores glucocorticoid sensitivity in a mouse model of neutrophilic airway inflammation. Mucosal Immunol. 2015;8:1212.

    Article  PubMed  CAS  Google Scholar 

  52. Chachi L, Gavrila A, Tliba O, Amrani Y. Abnormal corticosteroid signalling in airway smooth muscle: mechanisms and perspectives for the treatment of severe asthma. Clin Exp Allergy. 2015;45(11):1637–46.

    Article  PubMed  CAS  Google Scholar 

  53. Gagliardo R, Chanez P, Vignola AM, Bousquet J, Vachier I, Godard P, Bonsignore G, Demoly P, Mathieu M. Glucocorticoid receptor alpha and beta in glucocorticoid dependent asthma. Am J Respir Crit Care Med. 2000;162:7.

    Article  PubMed  CAS  Google Scholar 

  54. Hamid QA, Wenzel SE, Hauk PJ, Tsicopoulos A, Wallaert B, Lafitte JJ, Chrousos GP, Szefler SJ, Leung DY. Increased glucocorticoid receptor beta in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 1999;159:1600.

    Article  PubMed  CAS  Google Scholar 

  55. Butler CA, McQuaid S, Taggart CC, Weldon S, Carter R, Skibinski G, Warke TJ, Choy DF, McGarvey LP, Bradding P, Arron JR, Heaney LG. Glucocorticoid receptor beta and histone deacetylase 1 and 2 expression in the airways of severe asthma. Thorax. 2011;67:392–8.

    Article  PubMed  Google Scholar 

  56. Tliba O, Damera G, Banerjee A, Gu S, Baidouri H, Keslacy S, Amrani Y. Cytokines induce an early steroid resistance in airway smooth muscle cells: novel role of interferon regulatory factor-1. Am J Respir Cell Mol Biol. 2008;38:463.

    Article  PubMed  CAS  Google Scholar 

  57. O’Connell D, Bouazza B, Kokalari B, Amrani Y, Khatib A, Ganther JD, Tliba O. IFN-gamma-induced JAK/STAT, but not NF-kappaB, signaling pathway is insensitive to glucocorticoid in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2015;309:L348.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Salem S, Harris T, Mok JS, Li MY, Keenan CR, Schuliga MJ, Stewart AG. Transforming growth factor-beta impairs glucocorticoid activity in the A549 lung adenocarcinoma cell line. Br J Pharmacol. 2012;166:2036.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Keenan CR, Mok JS, Harris T, Xia Y, Salem S, Stewart AG. Bronchial epithelial cells are rendered insensitive to glucocorticoid transactivation by transforming growth factor-beta1. Respir Res. 2014;15:55.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Li M, Keenan CR, Lopez-Campos G, Mangum JE, Chen Q, Prodanovic D, Xia YC, Langenbach SY, Harris T, Hofferek V, Reid GE, Stewart AG. A non-canonical pathway with potential for safer modulation of transforming growth factor-beta1 in steroid-resistant airway diseases. iScience. 2019;12:232.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Xia YC, Radwan A, Keenan CR, Langenbach SY, Li M, Radojicic D, Londrigan SL, Gualano RC, Stewart AG. Glucocorticoid insensitivity in virally infected airway epithelial cells is dependent on transforming growth factor-beta activity. PLoS Pathog. 2017;13:e1006138.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. McKinley L, Alcorn JF, Peterson A, Dupont RB, Kapadia S, Logar A, Henry A, Irvin CG, Piganelli JD, Ray A, Kolls JK. TH17 cells mediate steroid-resistant airway inflammation and airway hyperresponsiveness in mice. J Immunol. 2008;181:4089.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Fei X, Zhang PY, Zhang X, Zhang GQ, Bao WP, Zhang YY, Zhang M, Zhou X. IL-17A monoclonal antibody partly reverses the glucocorticoids insensitivity in mice exposed to ozonec. Inflammation. 2017;40:788.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Zijlstra GJ, Ten Hacken NH, Hoffmann RF, van Oosterhout AJ, Heijink IH. Interleukin-17A induces glucocorticoid insensitivity in human bronchial epithelial cells. Eur Respir J. 2012;39:439.

    Article  PubMed  CAS  Google Scholar 

  65. Vazquez-Tello A, Semlali A, Chakir J, Martin JG, Leung DY, Eidelman DH, Hamid Q. Induction of glucocorticoid receptor-beta expression in epithelial cells of asthmatic airways by T-helper type 17 cytokines. Clin Exp Allergy. 2010;40:1312.

    Article  PubMed  CAS  Google Scholar 

  66. Marone G, Granata F, Pucino V, Pecoraro A, Heffler E, Loffredo S, Scadding GW, Varricchi G. The intriguing role of interleukin 13 in the pathophysiology of asthma. Front Pharmacol. 2019;10:1387.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Therien AG, Bernier V, Weicker S, Tawa P, Falgueyret JP, Mathieu MC, Honsberger J, Pomerleau V, Robichaud A, Stocco R, Dufresne L, Houshyar H, Lafleur J, Ramachandran C, O’Neill GP, Slipetz D, Tan CM. Adenovirus IL-13-induced airway disease in mice: a corticosteroid-resistant model of severe asthma. Am J Respir Cell Mol Biol. 2008;39:26.

    Article  PubMed  CAS  Google Scholar 

  68. Richter A, Puddicombe SM, Lordan JL, Bucchieri F, Wilson SJ, Djukanovic R, Dent G, Holgate ST, Davies DE. The contribution of interleukin (IL)-4 and IL-13 to the epithelial-mesenchymal trophic unit in asthma. Am J Respir Cell Mol Biol. 2001;25:385.

    Article  PubMed  CAS  Google Scholar 

  69. Spahn JD, Szefler SJ, Surs W, Doherty DE, Nimmagadda SR, Leung DY. A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol. 1996;157:2654.

    Article  PubMed  CAS  Google Scholar 

  70. Kabata H, Moro K, Fukunaga K, Suzuki Y, Miyata J, Masaki K, Betsuyaku T, Koyasu S, Asano K. Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation. Nat Commun. 2013;4:2675.

    Article  PubMed  CAS  Google Scholar 

  71. Liu S, Verma M, Michalec L, Liu W, Sripada A, Rollins D, Good J, Ito Y, Chu H, Gorska MM, Martin RJ, Alam R. Steroid resistance of airway type 2 innate lymphoid cells from patients with severe asthma: the role of thymic stromal lymphopoietin. J Allergy Clin Immunol. 2018;141:257.

    Article  PubMed  CAS  Google Scholar 

  72. Okayama Y, Okumura S, Sagara H, Yuki K, Sasaki T, Watanabe N, Fueki M, Sugiyama K, Takeda K, Fukuda T, Saito H, Ra C. FcepsilonRI-mediated thymic stromal lymphopoietin production by interleukin-4-primed human mast cells. Eur Respir J. 2009;34:425.

    Article  PubMed  CAS  Google Scholar 

  73. Shikotra A, Choy DF, Ohri CM, Doran E, Butler C, Hargadon B, Shelley M, Abbas AR, Austin CD, Jackman J, Wu LC, Heaney LG, Arron JR, Bradding P. Increased expression of immunoreactive thymic stromal lymphopoietin in patients with severe asthma. J Allergy Clin Immunol. 2012;129:104.

    Article  PubMed  CAS  Google Scholar 

  74. Cahill KN, Katz HR, Cui J, Lai J, Kazani S, Crosby-Thompson A, Garofalo D, Castro M, Jarjour N, DiMango E, Erzurum S, Trevor JL, Shenoy K, Chinchilli VM, Wechsler ME, Laidlaw TM, Boyce JA, Israel E. KIT inhibition by imatinib in patients with severe refractory asthma. N Engl J Med. 2017;376:1911.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Koziol-White CJ, Jia Y, Baltus GA, Cooper PR, Zaller DM, Crackower MA, Sirkowski EE, Smock S, Northrup AB, Himes BE, Alves SE, Panettieri RA Jr. Inhibition of spleen tyrosine kinase attenuates IgE-mediated airway contraction and mediator release in human precision cut lung slices. Br J Pharmacol. 2016;173:3080.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Phillips JE, Renteria L, Burns L, Harris P, Peng R, Bauer CM, Laine D, Stevenson CS. Btk inhibitor RN983 delivered by dry powder nose-only aerosol inhalation inhibits bronchoconstriction and pulmonary inflammation in the ovalbumin allergic mouse model of asthma. J Aerosol Med Pulm Drug Deliv. 2016;29:233.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Dispenza MC, Krier-Burris RA, Chhiba KD, Undem BJ, Robida PA, Bochner BS. Bruton’s tyrosine kinase inhibition effectively protects against human IgE-mediated anaphylaxis. J Clin Invest. 2020;130(9):4759–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Kim YY, Hur G, Lee SW, Lee SJ, Lee S, Kim SH, Rho MC. AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcepsilonRI/TGF-beta signaling pathway. Pharmacol Res. 2020;159:105027.

    Article  PubMed  CAS  Google Scholar 

  79. Maun HR, Jackman JK, Choy DF, Loyet KM, Staton TL, Jia G, Dressen A, Hackney JA, Bremer M, Walters BT, Vij R, Chen X, Trivedi NN, Morando A, Lipari MT, Franke Y, Wu X, Zhang J, Liu J, Wu P, Chang D, Orozco LD, Christensen E, Wong M, Corpuz R, Hang JQ, Lutman J, Sukumaran S, Wu Y, Ubhayakar S, Liang X, Schwartz LB, Babina M, Woodruff PG, Fahy JV, Ahuja R, Caughey GH, Kusi A, Dennis MS, Eigenbrot C, Kirchhofer D, Austin CD, Wu LC, Koerber JT, Lee WP, Yaspan BL, Alatsis KR, Arron JR, Lazarus RA, Yi T. An allosteric anti-tryptase antibody for the treatment of mast cell-mediated severe asthma. Cell. 2019;179:417.

    Article  PubMed  CAS  Google Scholar 

  80. Erlich TH, Sharkia I, Landolina N, Assayag M, Goldberger O, Berkman N, Levi-Schaffer F, Razin E. Modulation of allergic responses by mitochondrial STAT3 inhibitors. Allergy. 2018;73:2160.

    Article  PubMed  CAS  Google Scholar 

  81. Lin W, Su F, Gautam R, Wang N, Zhang Y, Wang X. Raf kinase inhibitor protein negatively regulates FcepsilonRI-mediated mast cell activation and allergic response. Proc Natl Acad Sci U S A. 2018;115:E9859.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Infection, Immunity and Inflammation, Clinical Sciences, University of Leicester, Leicester, UK

    Abdulrahman Alzahrani, Aamir Hussain, Fahad Alhadian, Jameel Hakeem, Sana Douaoui, Omar Tliba & Peter Bradding

  2. Department of Respiratory Sciences, University of Leicester, Leicester, UK

    Yassine Amrani

  3. Institute for Lung Health, Leicester Biomedical Research Center Respiratory, Leicester, UK

    Yassine Amrani

Authors
  1. Abdulrahman Alzahrani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aamir Hussain
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fahad Alhadian
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jameel Hakeem
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sana Douaoui
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Omar Tliba
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter Bradding
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yassine Amrani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yassine Amrani .

Editor information

Editors and Affiliations

  1. Department of Molecular & Cellular Physiology, Albany Medical College, Albany, NY, USA

    Yong-Xiao Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Alzahrani, A. et al. (2021). Potential Role of Mast Cells in Regulating Corticosteroid Insensitivity in Severe Asthma. In: Wang, YX. (eds) Lung Inflammation in Health and Disease, Volume I. Advances in Experimental Medicine and Biology, vol 1303. Springer, Cham. https://doi.org/10.1007/978-3-030-63046-1_1

Download citation

Publish with us

Policies and ethics

Search

Navigation