Gene transcription changes in asthmatic chronic rhinosinusitis with nasal polyps and comparison to those in atopic dermatitis.
BACKGROUND
Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease without effective medical treatment. Therefore, we sought to identify gene expression changes, particularly those occurring early, in aCRSwNP. To highlight expression changes associated with eosinophilic epithelial inflammation, we further compared the changes in aCRSwNP with those in a second eosinophilic epithelial disease, atopic dermatitis (AD), which is also closely related to asthma.


RESULTS
Genome-wide mRNA levels measured by exon array in both nasosinus inflamed mucosa and adjacent polyp from 11 aCRSwNP patients were compared to those in nasosinus tissue from 17 normal or rhinitis subjects without polyps. Differential expression of selected genes was confirmed by qRT-PCR or immunoassay, and transcription changes common to AD were identified. Comparison of aCRSwNP inflamed mucosa and polyp to normal/rhinitis tissue identified 447 differentially transcribed genes at > or = 2 fold-change and adjusted p-value < 0.05. These included increased transcription of chemokines localized to chromosome 17q11.2 (CCL13, CCL2, CCL8, and CCL11) that favor eosinophil and monocyte chemotaxis and chemokines (CCL18, CCL22, and CXCL13) that alternatively-activated monocyte-derived cells have been shown to produce. Additional transcription changes likely associated with Th2-like eosinophilic inflammation were prominent and included increased IL1RL1 (IL33 receptor) and EMR1&3 and decreased CRISP2&3. A down-regulated PDGFB-centric network involving several smooth muscle-associated genes was also implicated. Genes at 17q11.2, genes associated with alternative activation or smooth muscle, and the IL1RL1 gene were also differentially transcribed in AD.


CONCLUSIONS
Our data implicate several genes or gene sets in aCRSwNP and eosinophilic epithelial inflammation, some that likely act in the earlier stages of inflammation. The identified gene expression changes provide additional diagnostic and therapeutic targets for aCRSwNP and other eosinophilic epithelial diseases.
Plager
Douglas A
DA
Allergic Diseases Research Laboratory, Mayo Clinic, Rochester, Minnesota, United States of America. plager.douglas@mayo.edu
Kahl
Jane C
JC
Asmann
Yan W
YW
Nilson
Allan E
AE
Pallanch
John F
JF
Friedman
Oren
O
Kita
Hirohito
H
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000235:genetics*; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D054413:Chemokine CCL11 / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics; D054422:Chemokine CCL22 / Q000235:genetics; D054412:Chemokine CCL8 / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics; D003876:Dermatitis, Atopic / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics; D009077:Mucins / Q000235:genetics; D009298:Nasal Polyps / Q000378:metabolism* / Q000473:pathology*; D015531:Radioimmunoprecipitation Assay; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D018000:Receptors, Peptide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000235:genetics*; D012471:Salivary Proteins and Peptides / Q000235:genetics; D029589:Seminal Plasma Proteins / Q000235:genetics; D012852:Sinusitis / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D055815:Young Adult
C094471:ADGRE1 protein, human; C431147:ADGRE3 protein, human; C515456:CCL11 protein, human; C099677:CCL13 protein, human; C111792:CCL18 protein, human; C111835:CCL2 protein, human; C515482:CCL22 protein, human; C515453:CCL8 protein, human; C062621:CRISP2 protein, human; C489926:CRISP3 protein, human; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D054413:Chemokine CCL11; D018932:Chemokine CCL2; D054422:Chemokine CCL22; D054412:Chemokine CCL8; D019742:Chemokines, CC; D006023:Glycoproteins; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008562:Membrane Glycoproteins; D018945:Monocyte Chemoattractant Proteins; D009077:Mucins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D012471:Salivary Proteins and Peptides; D029589:Seminal Plasma Proteins