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Title: Effects of IL-13 on normal and asthmatic pediatric bronchial and nasal epithelial cells : IL-13 as a therapeutic target in childhood asthma
Author: Thavagnanam, Surendran
ISNI:       0000 0004 2745 3560
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2012
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Goblet cell hyperplasia (GCH) and decreased ciliogenesis are characteristic features which may be influenced by Th2 cytokines (eg IL-9 and IL-13). Studies have suggested nasal epithelium can be used as a surrogate for bronchial epithelial. AIM In vitro basal mucociliary differentiation and differences in paediatric epithelial cells (normal & asthmatics) exposed to IL-9 and IL-13 were studied. To study the feasibility of nasal epithelium as a replacement for bronchus. METHOD Bronchial (PBECs) and paired nasal brushings (PNECs) obtained from children were differentiated at air liquid interface for 28 days. Cells treated with IL-13, IL-9 or a combination of IL-9/-13. Transeplthelial resistance (TEER), number of ciliated and goblet cells, MUC5AC mRNA expression and relative absorbance of MUC5AC were assessed as a measure of tissue differentiation. RESULTS Asthmatic PBECs (PBEC(A)) had a significant GCH and fewer ciliated cells compared to normal PBEC, (PBEC(N) under un-stimulated conditions. Stimulation with 20ng/ml IL-13 in PBEC(N) and PBEC(A) resulted in GCH and decreased ciliated cell number compared to un-stimulated respective cultures. Similar was also observed in the increase of MUC5AC mRNA expression with 20ng/ml IL-13 in PBEC(A) and PBEC(N). IL-9 alone did not alter goblet cell numbers, however PBEC(N) with the IL-9/IL-13 increased goblet cell number compared with un-stimulated. IL-9 and IL-9/IL-13 stimulated PBEC(N) had reduced ciliated cell numbers compared with un-stimulated. In PBEC(A), only 20ng/ml IL-13 significantly reduced ciliated cell number compared with un-stimulated. Morphological differences observed between asthmatic and normal PNECs and PBECs was also supported by varied cytokine release and functional differences following IL-13 stimulation. CONCLUSION Morphological differences exist between normal and asthmatic PBECs and PNECs under un-stimulated conditions. IL-13 drives PBEC(N) towards an asthmatic phenotype and worsens the phenotype in PBEC(A) with reduced ciliated cell numbers and increased GCH. IL-9 alone did not stimulate GCH in PBEC(N), and showed no synergistic effect with IL-13 in driving GCH. IL-9 and IL-9/13 lowered the number of ciliated cells in PBEC(N), however this was not seen in asthmatic cells. Functional differences exist between PBEC and PNEC therefore questions the suitability of nasal epithelium as a surrogate.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available