Microarray analysis of distinct gene transcription profiles in non-eosinophilic chronic sinusitis with nasal polyps.
BACKGROUND
Recent literature has indicated the feasibility of microarray analysis in the characterization of chronic sinusitis. We hypothesized that previously unexplored inflammatory mechanisms would be involved in the pathophysiology of noneosinophilic chronic rhinosinusitis with nasal polyps (NE-CRSwNP) and that this technology could be used to identify the gene expression of these novel and previously known mediators.


METHODS
Patients with CRSwNP failing medical therapy were prospectively enrolled and NP tissue was removed at time of surgery. NE-CRSwNP was diagnosed based on clinical parameters including absence of allergic disease and confirmed with histopathology showing lack of eosinophilic infiltration. Messenger RNA (mRNA) transcripts extracted from study and control patients were then subjected to microarray analysis using Affymatrix based chips. Validation of findings was then confirmed via quantitative reverse transcription polymerase chain reaction (qRT-PCR).


RESULTS
Microarray analysis revealed activation of pathways involved in antigen presentation, cellular movement, hematopoiesis, carcinogenesis, apoptosis, and cell signaling. Previously unexplored genes of interest were identified and their differential regulation was validated via qRT-PCR. Our data showed up-regulation of innate inflammation genes (IL-6, IL-8, and monocyte chemoattractant protein 1), hypoxia-induced inflammation 1alpha, and fibrosis (tenascin) and lack of up-regulation of genes associated with allergic, eosinophilic inflammation (IL-4 and IL-13). Additionally, the genes for CXCL1 and autocrine motility factor receptor were novelly identified to be up-regulated.


CONCLUSIONS
This study explores the utility of gene microarray technology in identifying unexplored targets of immune dysregulation in NE-CRSwNP. Furthermore, the data characterize the immunologic profile of NE-CRSwNP as it differs from other forms of CRSwNP, in particular, those known to be associated with eosinophilic inflammation.
Payne
Spencer C
SC
Department of Otolaryngology-Head and Neck Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA. spencer.payne@virginia.edu
Han
Joseph K
JK
Huyett
Phillip
P
Negri
Julie
J
Kropf
Elizabeth Z
EZ
Borish
Larry
L
Steinke
John W
JW
D002908:Chronic Disease; D006801:Humans; D046228:Microarray Analysis; D009298:Nasal Polyps / Q000150:complications*; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012220:Rhinitis / Q000235:genetics; D012852:Sinusitis / Q000235:genetics*; D014158:Transcription, Genetic