Expression profiling of inflammatory mediators in pediatric sinus mucosa.
OBJECTIVE
To evaluate gene expression by microarray analyses of inflammatory mediators in the sinus mucosa of children with and without chronic rhinosinusitis (CRS).


METHODS
Prospective molecular genetics analysis.


METHODS
Children's National Medical Center, Washington, DC.


METHODS
Eleven patients with CRS who underwent endoscopic sinus surgery and 10 control children who underwent craniofacial resection or neurosurgical procedures.


METHODS
Gene expression levels of sinus tissue from 6 patients with CRS and 6 controls and messenger RNA expression levels of upregulated inflammatory/immune response genes, as well as cytokines of interest, determined by quantitative reverse transcription-polymerase chain reaction.


RESULTS
Gene expression using the Plier algorithm yielded the most consistent grouping of samples: 96 genes were significantly upregulated more than 2-fold, and 123 genes were downregulated by at least 50% in the CRS sinus tissues compared with controls (P < .05). GeneSpring analysis demonstrated significant changes in several ontology categories in the CRS samples, including inflammatory/immune response genes. The chemokines CXCL13 and CXCL5, serum amyloid A, serpin B4, and defensin beta1 were highly upregulated (> or =5-fold). Increased expression of these genes was validated by quantitative reverse transcription-polymerase chain reaction in an independent set of tissues. Expression levels of interleukins 5, 6, and 8 were similar in both cohorts; these results were validated by reverse transcription-polymerase chain reaction.


CONCLUSIONS
Microarray analyses of sinus mucosa in children with CRS showed an increased expression of inflammatory genes involved in innate and adaptive immune systems. This technology can be successfully used to identify genes implicated in the pathogenesis of pediatric CRS.
Wu
Xiaofang
X
Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC 20010, USA.
Ghimbovschi
Svetlana
S
Aujla
Pawandeep K
PK
Rose
Mary C
MC
Peña
Maria T
MT
D000293:Adolescent; D000951:Antigens, Neoplasm / Q000235:genetics*; D054382:Chemokine CXCL13 / Q000235:genetics*; D054365:Chemokine CXCL5 / Q000235:genetics*; D002648:Child; D002908:Chronic Disease; D004724:Endoscopy; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008297:Male; D009297:Nasal Mucosa / Q000473:pathology; D019635:Neurosurgical Procedures / Q000379:methods; D013517:Otorhinolaryngologic Surgical Procedures / Q000295:instrumentation; D016133:Polymerase Chain Reaction; D012220:Rhinitis / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D015843:Serpins / Q000235:genetics*; D000685:Serum Amyloid A Protein / Q000235:genetics*
D000951:Antigens, Neoplasm; D054382:Chemokine CXCL13; D054365:Chemokine CXCL5; D007378:Interleukins; D015843:Serpins; D000685:Serum Amyloid A Protein; C051072:squamous cell carcinoma-related antigen