- Title
- Mediators of neutrophil function in children with protracted bacterial bronchitis
- Creator
- Baines, Katherine J.; Upham, John W.; Yerkovich, Stephanie T.; Chang, Anne B.; Marchant, Julie M.; Carroll, Melanie; Simpson, Jodie L.; Gibson, Peter G.
- Relation
- NHMRC.569240, 511019, 545216 and 1042601
- Relation
- Chest Vol. 146, Issue 4, p. 1013-1020
- Publisher Link
- http://dx.doi.org/10.1378/chest.14-0131
- Publisher
- American College of Chest Physicians
- Resource Type
- journal article
- Date
- 2014
- Description
- Background: Protracted bacterial bronchitis (PBB) is a common and treatable cause of chronic wet cough in children in which the mechanisms are not understood. This study investigates the IL-1 pathway and a neutrophil gene expression signature in PBB. Methods: BAL was collected from children in an experimental cohort (n = 21, PBB; n = 33, control subjects), and a second validation cohort (n = 36, PBB; n = 11, control subjects). IL-1β, IL-1 receptor antagonist (IL-1RA), and α-defensins 1-3 were assayed by enzyme-linked immunosorbent assay, western blot, and quantitative real-time polymerase chain reaction, together with selected IL-1 pathway members and neutrophil-related molecules. Results: In the experimental cohort, children with symptomatic PBB had significantly higher levels of IL-1β and α-defensin gene and protein expression. Expression of the neutrophil chemokine receptor C-X-C motif receptor 2 was also higher in PBB. IL-1RA protein was higher, however, the IL-1RA:IL-1β ratio was lower in children with PBB than control subjects. In the validation cohort, protein and gene expression of IL-1β and α-defensins 1-3 were confirmed higher, as was gene expression of IL-1 pathway members and C-X-C motif receptor 2. IL-1β and α-defensin 1-3 levels lowered when PBB was treated and resolved. In children with recurrent PBB, gene expression of the IL-1β signaling molecules pellino-1 and IL-1 receptor-associated kinase 2 was significantly higher. IL-1β protein levels correlated with BAL neutrophilia and the duration and severity of cough symptoms. IL-1β and α-defensin 1-3 levels were highly correlated. Conclusions: PBB is characterized by increased IL-1β pathway activation. IL-1β and related mediators were associated with BAL neutrophils, cough symptoms, and disease recurrence, providing insight into PBB pathogenesis.
- Subject
- protracted bacterial bronchitis (PBB); children; IL-1 pathway; neutrophil gene expression signature
- Identifier
- http://hdl.handle.net/1959.13/1301485
- Identifier
- uon:20295
- Identifier
- ISSN:0012-3692
- Language
- eng
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