Expression Profiling of Inflammatory Mediators in Pediatric Sinus Mucosa

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Abstract

Objective

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

Design

Prospective molecular genetics analysis.

Setting

Children's National Medical Center, Washington, DC.

Subjects

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

Main Outcome Measures

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 β1 were highly upregulated (≥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.

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