1. Role for NLRP3 Inflammasome–mediated, IL-1β–Dependent Responses in Severe, Steroid-Resistant Asthma
- Author
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Jodie L. Simpson, Lisa Wood, Jay C. Horvat, M Khadem Ali, Katherine J. Baines, James W. Pinkerton, Jeremy A. Hirota, Mark E. Cooper, Malcolm R. Starkey, Peter G. Gibson, Darryl A. Knight, Avril A. B. Robertson, Philip M. Hansbro, Ama Tawiah Essilfie, Alexandra C. Brown, Peter A. B. Wark, Richard Kim, Jemma R. Mayall, Luke A. J. O'Neill, and Nicole G. Hansbro
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Chlamydia ,business.industry ,Inflammasome ,Disease ,Critical Care and Intensive Care Medicine ,medicine.disease ,Pyrin domain ,Pathogenesis ,03 medical and health sciences ,030104 developmental biology ,Immunology ,medicine ,Respiratory system ,Receptor ,business ,medicine.drug ,Asthma - Abstract
Rationale: Severe, steroid-resistant asthma is the major unmet need in asthma therapy. Disease heterogeneity and poor understanding of pathogenic mechanisms hampers the identification of therapeutic targets. Excessive nucleotide-binding oligomerization domain–like receptor family, pyrin domain–containing 3 (NLRP3) inflammasome and concomitant IL-1β responses occur in chronic obstructive pulmonary disease, respiratory infections, and neutrophilic asthma. However, the direct contributions to pathogenesis, mechanisms involved, and potential for therapeutic targeting remain poorly understood, and are unknown in severe, steroid-resistant asthma.Objectives: To investigate the roles and therapeutic targeting of the NLRP3 inflammasome and IL-1β in severe, steroid-resistant asthma.Methods: We developed mouse models of Chlamydia and Haemophilus respiratory infection–mediated, ovalbumin-induced severe, steroid-resistant allergic airway disease. These models share the hallmark features of human disease, including ele...
- Published
- 2017