Cellular mechanisms underlying steroid-resistant asthma

被引:83
作者
Wadhwa, Ridhima [1 ,2 ]
Dua, Kamal [1 ,2 ,3 ,4 ]
Adcock, Ian M. [5 ]
Horvat, Jay C. [3 ,4 ]
Kim, Richard Y. [1 ,3 ,4 ,6 ]
Hansbro, Philip M. [1 ,3 ,4 ,6 ]
机构
[1] Centenary Inst, Ctr Inflammat, Sydney, NSW, Australia
[2] Univ Technol Sydney, Grad Sch Hlth, Discipline Pharm, Sydney, NSW, Australia
[3] Univ Newcastle, Prior Res Ctr Hlth Lungs, Newcastle, NSW, Australia
[4] Hunter Med Res Inst, Newcastle, NSW, Australia
[5] Imperial Coll London, Natl Heart & Lung Inst, Airways Dis Sect, London, England
[6] Univ Technol Sydney, Fac Sci, Sydney, NSW, Australia
基金
英国医学研究理事会;
关键词
HISTONE DEACETYLASE ACTIVITY; ALLERGIC AIRWAYS DISEASE; GLUCOCORTICOID-RECEPTOR; RESPIRATORY-INFECTION; NLRP3; INFLAMMASOME; PARTICULATE MATTER; MACROLIDE THERAPY; EPITHELIAL-CELLS; INDUCED SPUTUM; RESPONSES;
D O I
10.1183/16000617.0096-2019
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults. Several clinical and experimental studies have revealed associations between specific respiratory infections and steroid-resistant asthma in adults. Here, we discuss recent findings from other authors as well as our own studies that have developed novel experimental models for interrogating the association between respiratory infections and severe steroid-resistant asthma. These models have enabled the identification of new therapies using macrolides, as well as several novel disease mechanisms, including the microRNA-21/phosphoinositide 3-kinase/histone deacetylase 2 axis and NLRP3 inflammasomes, and highlight the potential of these mechanisms as therapeutic targets.
引用
收藏
页数:10
相关论文
共 101 条
[11]   Glucocorticoid resistance in inflammatory diseases [J].
Barnes, Peter J. ;
Adcock, Ion M. .
LANCET, 2009, 373 (9678) :1905-1917
[12]   DRUG-THERAPY - INHALED GLUCOCORTICOIDS FOR ASTHMA [J].
BARNES, PJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 332 (13) :868-875
[13]   Rhinovirus-induced IL-25 in asthma exacerbation drives type 2 immunity and allergic pulmonary inflammation [J].
Beale, Janine ;
Jayaraman, Annabelle ;
Jackson, David J. ;
Macintyre, Jonathan D. R. ;
Edwards, Michael R. ;
Walton, Ross P. ;
Zhu, Jie ;
Ching, Yee Man ;
Shamji, Betty ;
Edwards, Matt ;
Westwick, John ;
Cousins, David J. ;
Hwang, You Yi ;
McKenzie, Andrew ;
Johnston, Sebastian L. ;
Bartlett, Nathan W. .
SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (256)
[14]   Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma [J].
Bel, Elisabeth H. ;
Wenzel, Sally E. ;
Thompson, Philip J. ;
Prazma, Charlene M. ;
Keene, Oliver N. ;
Yancey, Steven W. ;
Ortega, Hector G. ;
Pavord, Ian D. .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (13) :1189-1197
[15]   Trial of roxithromycin in subjects with asthma and serological evidence of infection with Chlamydia pneumoniae [J].
Black, PN ;
Blasi, F ;
Jenkins, CR ;
Scicchitano, R ;
Mills, GD ;
Rubinfeld, AR ;
Ruffin, RE ;
Mullins, PR ;
Dangain, J ;
Cooper, BC ;
David, DB ;
Allegra, L .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2001, 164 (04) :536-541
[16]   Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33 [J].
Christianson, Christina A. ;
Goplen, Nicholas P. ;
Zafar, Iram ;
Irvin, Chaoyu ;
Good, James T., Jr. ;
Rollins, Donald R. ;
Gorentla, Balachandra ;
Liu, Weimin ;
Gorska, Magdalena M. ;
Chu, HongWei ;
Martin, Richard J. ;
Alam, Rafeul .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2015, 136 (01) :59-U142
[17]   A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases [J].
Coll, Rebecca C. ;
Robertson, Avril A. B. ;
Chae, Jae Jin ;
Higgins, Sarah C. ;
Munoz-Planillo, Raul ;
Inserra, Marco C. ;
Vetter, Irina ;
Dungan, Lara S. ;
Monks, Brian G. ;
Stutz, Andrea ;
Croker, Daniel E. ;
Butler, Mark S. ;
Haneklaus, Moritz ;
Sutton, Caroline E. ;
Nunez, Gabriel ;
Latz, Eicke ;
Kastner, Daniel L. ;
Mills, Kingston H. G. ;
Masters, Seth L. ;
Schroder, Kate ;
Cooper, Matthew A. ;
O'Neill, Luke A. J. .
NATURE MEDICINE, 2015, 21 (03) :248-+
[18]   Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages [J].
Cosio, BG ;
Tsaprouni, L ;
Ito, K ;
Jazrawi, E ;
Adcock, IM ;
Barnes, PJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (05) :689-695
[19]   Long-term macrolide therapy in chronic inflammatory airway diseases [J].
Crosbie, P. A. J. ;
Woodhead, M. A. .
EUROPEAN RESPIRATORY JOURNAL, 2009, 33 (01) :171-181
[20]   Effect of the purinergic receptor P2X7 on Chlamydia infection in cervical epithelial cells and vaginally infected mice [J].
Darville, Toni ;
Welter-Stahl, Lynn ;
Cruz, Cristiane ;
Sater, Ali Abdul ;
Andrews, Charles W., Jr. ;
Ojcius, David M. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (06) :3707-3714