Abstract
Original language | English |
---|---|
Pages (from-to) | 1-11 |
Number of pages | 11 |
Journal | European Respiratory Journal |
Volume | 4 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2018 |
Fingerprint
Cite this
}
Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis. / Chen , Alice C-H; Tran, Hai B. ; Xi , Yang; Yerkovich, Stephanie; J. Baines, Katherine ; Pizzutto, Susan; Carroll, Melanie; Robertson, Avril A.B. ; Cooper, Matthew A.; Schroder, Kate ; Simpson, Jodie L. ; Gibson, Peter G.; Hodge, Greg ; Masters, Ian B.; Buntain, Helen M. ; Petsky, Helen L.; Prime, Samantha J. ; Chang, Anne; Hodge, Sandra; Upham, John W.
In: European Respiratory Journal, Vol. 4, No. 1, 2018, p. 1-11.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Multiple inflammasomes may regulate the interleukin-1-driven inflammation in protracted bacterial bronchitis
AU - Chen , Alice C-H
AU - Tran, Hai B.
AU - Xi , Yang
AU - Yerkovich, Stephanie
AU - J. Baines, Katherine
AU - Pizzutto, Susan
AU - Carroll, Melanie
AU - Robertson, Avril A.B.
AU - Cooper, Matthew A.
AU - Schroder, Kate
AU - Simpson, Jodie L.
AU - Gibson, Peter G.
AU - Hodge, Greg
AU - Masters, Ian B.
AU - Buntain, Helen M.
AU - Petsky, Helen L.
AU - Prime, Samantha J.
AU - Chang, Anne
AU - Hodge, Sandra
AU - Upham, John W.
PY - 2018
Y1 - 2018
N2 - 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.
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.
U2 - 10.1183/23120541.00130-2017
DO - 10.1183/23120541.00130-2017
M3 - Article
VL - 4
SP - 1
EP - 11
JO - European Respiratory Journal
JF - European Respiratory Journal
SN - 0903-1936
IS - 1
ER -