Fungal allergens induce cathelicidin LL-37 expression in chronic rhinosinusitis patients in a nasal explant model.
BACKGROUND
Fungus is thought to play an important role in some subgroups of chronic rhinosinusitis (CRS) patients with eosinophilic mucus (EMCRS). The cathelicidin LL-37 is an important innate defense peptide with antimicrobial activity but its responses in CRS and EMCRS patients have not been established. We investigated the innate immune responses of LL-37 in nasal tissue from CRS and EMCRS patients to fungal allergen challenge.


METHODS
The levels of LL-37 produced by nasal tissue and secreted in response to fungal allergen challenge were determined by a nasal tissue explant in vitro model. LL-37 mRNA and protein levels were quantified by real-time reverse-transcriptase-polymerase chain reaction and immunoassay methods.


RESULTS
LL-37 mRNA expression in CRS, but not EMCRS patients, is significantly upregulated by Aspergillus (mean fourfold increase) and Alternaria (mean sixfold increase) extracts in a dose-response manner (p < 0.001). LL-37 peptide levels in the nasal tissue from CRS patients are increased in response to Alternaria (p < 0.05). In contrast, with EMCRS patients, the expression of LL-37 peptide in nasal tissue is increased with Aspergillus (p < 0.001) but is reduced with Alternaria. We also observed a trend where levels of secreted LL-37 were decreased with higher doses of Alternaria and Aspergillus extracts.


CONCLUSIONS
LL-37 is significantly up-regulated at the mRNA and protein level in CRS patients in response to fungal allergens. However, EMCRS patients do not show increased LL-37 at either the mRNA or the protein level in response to Alternaria.
Ooi
Eng Hooi
EH
Department of Surgery-Otorhinolaryngology Head and Neck Surgery, University of Adelaide and Flinders University, Adelaide, Australia.
Wormald
Peter-John
PJ
Carney
A Simon
AS
James
Craig Lloyd
CL
Tan
Lor Wai
LW
D000485:Allergens; D000528:Alternaria / Q000302:isolation & purification; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D001230:Aspergillus / Q000302:isolation & purification; D001706:Biopsy; D002478:Cells, Cultured; D005658:Fungi; D006801:Humans; D008070:Lipopolysaccharides; D005810:Multigene Family; D010256:Paranasal Sinuses / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics; D012220:Rhinitis / Q000235:genetics / Q000382:microbiology / Q000473:pathology / Q000601:surgery*; D012852:Sinusitis / Q000235:genetics / Q000382:microbiology / Q000473:pathology / Q000601:surgery*; D015854:Up-Regulation; D054804:Cathelicidins
D000485:Allergens; D023181:Antimicrobial Cationic Peptides; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D054804:Cathelicidins