Microarray Gene Analysis of Toll-Like Receptor Signaling Elements in Chronic Rhinosinusitis with Nasal Polyps

Abstract

Objective: To identify the regulatory mechanisms of Toll- like receptor (TLR)-associated genes in chronic rhinosinusitis (CRS) with nasal polyps (NP) using gene microarray analyses. Methods: We pooled: (1) NP biopsy specimens from 10 nonatopic CRS patients and (2) healthy mucosal tissue from 10 additional nonatopic healthy patients (controls). These pooled samples were evaluated by gene microarrays that included 125 genes for TLRs and associated signaling elements. To validate gene product expressions, 20 NP and 15 normal nasal turbinate tissues were evaluated for TLR-9 expression by immunohistochemical staining and Western blots using samples from gland cells, epithelial cells, and mononuclear cells cytologically identified by HE staining. Results: In pooled NP samples compared to pooled controls, 4 genes were upregulated (≧2-fold higher expression) and 19 were downregulated (≤0.5-fold lower expression). TLR-9 was an upregulated gene in NP tissue. Compared to control tissue, there were significantly higher percentages of TLR-9 positively stained NP gland cells, epithelial cells, and mononuclear cells (p < 0.001). On Western blots, while both normal and NP tissues expressed TLR-9 protein, the expression was significantly more pronounced for NP tissue (p < 0.001). Conclusions: Inflammation associated with CRS may be due to dysregulated innate immune elements, particularly TLR-9 and its associated signal transduction elements, which may impact upon prolonged activation of adaptive immune responses in the sinonasal mucosa.

Functional Effects of Toll-Like Receptor (TLR)3, 7, 9, RIG-I and MDA-5 Stimulation in Nasal Epithelial Cells

“…Presently, CpG stimulation of the nasal mucosa significantly increased IL-8 secretion, whereas no such thing was seen in supernatants from the epithelial cells. Zhao et al have reported that TLR9 is highly up-regulated in CRS patients with nasal polyps [44]. This indicates that also TLR9 activation could have an important role in exacerbation of inflammatory airway diseases like CRS.…”

Differential Expression of Innate Immunity Genes in Chronic Rhinosinusitis

“…These systems work in conjunction and the adaptive immune system may be activated by various components of the innate immune system. [4][5][6] Alterations in innate immune gene expression have been shown in patients with CRSwNP, 6,10,12,14,16,17 but there is less literature regarding the role of the innate immune system in CRSsNP. Our objective was to expand the current literature by investigating both patients with and without NP.…”

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

“…Zhao et al 937 found that both TLR-9 mRNA and protein level were increased in NPs of CRSwNP compared to nasal tissue of controls. Last, Månsson et al 938 found that the NLR mRNA level was higher in NPs than in normal nasal mucosa.…”