title: Effects of IL-13 on mucociliary differentiation of pediatric asthmatic bronchial epithelial cells.
abstract: Goblet cell hyperplasia (GCH) and decreased ciliated cells are characteristic of asthma. We examined the effects of IL-13 (2 and 20 ng/mL) on in vitro mucociliary differentiation in pediatric bronchial epithelial cells (PBECs) of normal PBEC [PBEC(N)] and asthmatic PBEC [PBEC(A)] children. Markers of differentiation, real-time PCR for MUC5AC, MUC5AC ELISA, and transepithelial electrical resistance (TEER) were assessed. Stimulation with 20 ng/mL IL-13 in PBEC(N) resulted in GCH [20 ng/mL IL-13: mean, 33.8% (SD, 7.2) versus unstimulated: mean, 18.9% (SD, 5.0); p < 0.0001] and decreased ciliated cell number [20 ng/mL IL-13: mean, 8% (SD, 5.6) versus unstimulated: mean, 22.7% (SD,7.6); p < 0.01]. PBEC(N) stimulated with 20 ng/mL IL-13 resulted in >5-fold (SD, 3.2) increase in MUC5AC mRNA expression, p < 0.001, compared with unstimulated PBEC(N). In PBEC(A), GCH was also seen [20 ng/mL IL-13: mean, 44.7% (SD, 16.4) versus unstimulated: mean, 30.4% (SD, 13.9); p < 0.05] with a decreased ciliated cell number [20 ng/mL IL-13: mean, 8.8% (SD, 7.5) versus unstimulated: mean, 16.3% (SD, 4.2); p < 0.001]. We also observed an increase in MUC5AC mRNA expression with 20 ng/mL IL-13 in PBEC(A), p < 0.05. IL-13 drives PBEC(N) toward an asthmatic phenotype and worsens the phenotype in PBEC(A) with reduced ciliated cell numbers and increased goblet cells.
authors.affiliation: Centre for Infection and Immunity, Queen's University Belfast, Belfast BT12 6BN, Northern Ireland, United Kingdom.
authors.forename: Surendran
authors.initials: S
authors.lastname: Thavagnanam
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Parker
authors.forename: Michael E
authors.initials: ME
authors.lastname: McBrien
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Skibinski
authors.forename: Liam G
authors.initials: LG
authors.lastname: Heaney
authors.forename: Michael D
authors.initials: MD
authors.lastname: Shields
mesh_terms: D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002923:Cilia / Q000276:immunology / Q000473:pathology; D017097:Electric Impedance; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D020397:Goblet Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D018613:Microscopy, Confocal; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D009079:Mucociliary Clearance; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018793:Interleukin-13; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D011994:Recombinant Proteins