RT Journal Article
SR Electronic
T1 Late-breaking abstract: Increased IL-33 expression is related to high levels of TLR-2 and -4 in steroid-free subjects with asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P1800
VO 44
IS Suppl 58
A1 Asger Sverrild
A1 Katherine Baines
A1 Vibeke Backer
A1 Peter Gibson
A1 Celeste Porsbjerg
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P1800.abstract
AB Background: IL-33 is released as a consequence of infection or trauma to airway epithelium, and promotes Th2 type immunity, eosinophilic inflammation and mast cell activation. Toll like receptors (TLR) can be triggered by both pathogens and inhaled allergens, and TLR-4 signaling results in generation of IL-33 in mice. However, only little in vivo evidence is available in humans.Aim: We hypothesized increased expression of IL-33 to be associated with TLR expression in subjects with asthma.Methods: 19 steroid-free asthma patients with at least one objective marker of asthma (AHR to mannitol or methacholine, or reversibility to beta-2-agonist) and 9 healthy controls had airway mucosa biopsies taken. IL-33, TLR-2 and TLR-4 mRNA expression using real-time PCR was measured in the airway biopsies. Results were calculated as relative expression levels as compared to the housekeeping gene β-actin and the healthy control group.Results: Subjects with asthma had significantly higher gene expression of IL-33 compared to healthy controls (median [IQR]: 1.12 [0.82-1.59] vs. 0.86 [0.59-0.99], p=0.02). The expression of IL-33 was significantly increased in asthmatics with high TLR-2 and TLR-4 expression compared to low expression (median [IQR]: 1.06 [0.62-1.15] vs. 1.59 [1.07-1.95], p=0.02 and 0.82 [0.62-1.15] vs. 1.59 [1.11-1.95], p=0.003). Gene expression of IL-33, and TLR-2 and TLR-4 were highly correlated (rho(s)=0.61, p=0.005 and rho(s)=0.72, p=0.001).Conclusion: IL-33 is up-regulated in asthmatics with a high TLR-2 and -4 airway gene expression. This potentially links recognition of epithelial damage through TLR's and a Th2-skewed inflammatory response mediated by IL-33.