Fungal allergens induce cathelicidin LL-37 expression in chronic rhinosinusitis patients in a nasal explant model

EH Ooi, PJ Wormald, AS Carney… - American journal of …, 2007 - journals.sagepub.com
EH Ooi, PJ Wormald, AS Carney, CL James, LW Tan
American journal of rhinology, 2007journals.sagepub.com
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 …
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.
Conclusion
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.
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