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.
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 CRSpatients 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 CRSpatients 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.
Authors: Jivianne T Lee; Oswaldo H Escobar; Rabin Anouseyan; Agnieszka Janisiewicz; Edward Eivers; Keith E Blackwell; David B Keschner; Rohit Garg; Edith Porter Journal: Int Forum Allergy Rhinol Date: 2014-09-07 Impact factor: 3.858
Authors: Robert J Lee; Jennifer M Kofonow; Philip L Rosen; Adam P Siebert; Bei Chen; Laurel Doghramji; Guoxiang Xiong; Nithin D Adappa; James N Palmer; David W Kennedy; James L Kreindler; Robert F Margolskee; Noam A Cohen Journal: J Clin Invest Date: 2014-02-17 Impact factor: 14.808
Authors: Jeremiah A Alt; Xuan Qin; Abigail Pulsipher; Quinn Orb; Richard R Orlandi; Jianxing Zhang; Austin Schults; Wanjian Jia; Angela P Presson; Glenn D Prestwich; Siam Oottamasathien Journal: Int Forum Allergy Rhinol Date: 2015-09-08 Impact factor: 3.858