RT Journal Article
SR Electronic
T1 Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00130-2017
DO 10.1183/23120541.00130-2017
VO 4
IS 1
A1 Alice C-H. Chen
A1 Hai B. Tran
A1 Yang Xi
A1 Stephanie T. Yerkovich
A1 Katherine J. Baines
A1 Susan J. Pizzutto
A1 Melanie Carroll
A1 Avril A.B. Robertson
A1 Matthew A. Cooper
A1 Kate Schroder
A1 Jodie L. Simpson
A1 Peter G. Gibson
A1 Greg Hodge
A1 Ian B. Masters
A1 Helen M. Buntain
A1 Helen L. Petsky
A1 Samantha J. Prime
A1 Anne B. Chang
A1 Sandra Hodge
A1 John W. Upham
YR 2018
UL http://openres.ersjournals.com/content/4/1/00130-2017.abstract
AB Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1β expression and infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood.We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1β axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi.In healthy adult PBMCs, CD14+ monocytes contributed to 95% of total IL-1β-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1β expression (p<0.001), but decreased NLRC4 expression (p<0.01). NTHi induced IL-1β secretion in PBMCs from both healthy controls and patients with recurrent PBB. This was inhibited by Z-YVAD-FMK (a caspase-1 selective inhibitor) and by MCC950 (a NLRP3 selective inhibitor). In PBB BAL macrophages inflammasome complexes were visualised as fluorescence specks of NLRP3 or AIM2 colocalised with cleaved caspase-1 and cleaved IL-1β. NTHi stimulation induced formation of specks of cleaved IL-1β, NLRP3 and AIM2 in PBMCs, blood monocytes and monocyte-derived macrophages.We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1β-dominated inflammation in PBB.Airway IL-1β activation in protracted bacterial bronchitis http://ow.ly/ut9r30iqim2