Immunomodulatory innate defence regulator (IDR) peptide alleviates airway inflammation and hyper-responsiveness

Thorax
Hadeesha PiyadasaNeeloffer Mookherjee

Abstract

Exacerbation in asthma is associated with decreased expression of specific host defence peptides (HDPs) in the lungs. We examined the effects of a synthetic derivative of HDP, innate defence regulator (IDR) peptide IDR-1002, in house dust mite (HDM)-challenged murine model of asthma, in interleukin (IL)-33-challenged mice and in human primary bronchial epithelial cells (PBECs). IDR-1002 (6 mg/kg per mouse) was administered (subcutaneously) in HDM-challenged and/or IL-33-challenged BALB/c mice. Lung function analysis was performed with increasing dose of methacholine by flexiVent small animal ventilator, cell differentials in bronchoalveolar lavage performed by modified Wright-Giemsa staining, and cytokines monitored by MesoScale Discovery assay and ELISA. PBECs stimulated with tumour necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ), with or without IDR-1002, were analysed by western blots. IDR-1002 blunted HDM challenge-induced airway hyper-responsiveness (AHR), and lung leucocyte accumulation including that of eosinophils and neutrophils, in HDM-challenged mice. Concomitantly, IDR-1002 suppressed HDM-induced IL-33 in the lungs. IFN-γ/TNF-α-induced IL-33 production was abrogated by IDR-1002 in PBECs. Administration of...Continue Reading

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Citations

Feb 29, 2020·Nature Reviews. Drug Discovery·Neeloffer MookherjeeDonald J Davidson
Sep 26, 2020·Frontiers in Immunology·Mahadevappa HemshekharNeeloffer Mookherjee
Feb 20, 2019·Frontiers in Chemistry·Evan F HaneyRobert E W Hancock
Aug 26, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Hadeesha PiyadasaNeeloffer Mookherjee
Feb 26, 2021·Mediators of Inflammation·Guochun OuMei Zeng
Sep 1, 2021·Peptides·Ernesto M MartellAnselmo J Otero-González

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