Gene‐expression profiles in human nasal polyp tissues and identification of genetic susceptibility in aspirin‐intolerant asthma

Sekigawa, Takashi; Tajima, Atsushi; Hasegawa, Takashi; Hasegawa, Yoshinori; Inoue, Hiromasa; Sugiyama, Yasuyuki; Matsune, Shoji; Kurono, Yuichi; Inoue, Ituro

doi:10.1111/j.1365-2222.2009.03229.x

Cited by 37 publications

(23 citation statements)

References 31 publications

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“…It has recently been shown that the innate immune system has considerable specificity and the ability to discriminate between pathogens and self. Previous studies of NP using cDNA microarray technology have identified differentially expressed genes involved with inflammatory processes on a ‘global’ level [3,4] and components of adaptive immunity in particular [5,6,7]. In contrast with these studies, the aim of this exploratory study was to determine if there were any differentially expressed genes in NP of nonatopic CRS patients that were associated with TLRs and their signaling elements.…”

Section: Discussionmentioning

confidence: 66%

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

Zhao

Wang

Liu

et al. 2011

Int Arch Allergy Immunol

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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.

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Section: Discussionmentioning

confidence: 66%

“…Studies using cDNA microarray technology have identified differentially expressed genes involved with inflammatory processes on a ‘global’ level [3,4] and, in particular, components of adaptive immunity [5,6,7]. However, innate immune responses in the sinonasal mucosa in CRS have not been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

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

Zhao

Wang

Liu

et al. 2011

Int Arch Allergy Immunol

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“…It is noteworthy that IL-1R2 was detectable in microarrays of whole lung tissue (IL-1R2 expression was "present" in 98.8% of subjects). IL-1R2 has been shown to be associated with aspirin-induced asthma, both at the level of gene expression in human nasal polyps and as SNP associations (68). In another study, IL-1R2 SNPs were associated with atopy and showed interaction with early childhood virus infection (69).…”

Section: Discussionmentioning

confidence: 94%

Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

Luo

Obeidat

Narzo

et al. 2016

Am J Respir Cell Mol Biol

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Genome-wide association studies (GWASs) have identified loci that are robustly associated with asthma and related phenotypes; however, the molecular mechanisms underlying these associations need to be explored. The most relevant tissues to study the functional consequences of asthma are the airways. We used publically available data to derive expression quantitative trait loci (eQTLs) for human epithelial cells from small and large airways and applied the eQTLs in the interpretation of GWAS results of asthma and related phenotypes. For the small airways (n = 105), we discovered 660 eQTLs at a 10% false discovery rate (FDR), among which 315 eQTLs were not previously reported in a large-scale eQTL study of whole lung tissue. A large fraction of the identified eQTLs is supported by data from Encyclopedia of DNA Elements (ENCODE) showing that the eQTLs reside in regulatory elements (57.5 and 67.6% of cis-and trans-eQTLs, respectively). Published pulmonary GWAS hits were enriched as airway epithelial eQTLs (9.2-fold). Further, genes regulated by asthma GWAS loci in epithelium are significantly enriched in immune response pathways, such as IL-4 signaling (FDR, 5.2 3 10 24 ). The airway epithelial eQTLs described in this study are complementary to previously reported lung eQTLs and represent a powerful resource to link GWAS-associated variants to their regulatory function and thus elucidate the molecular mechanisms underlying asthma and airway-related conditions.

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“…This is the first description of an association of IL1R2 polymorphisms with atopy and the first report of rs740044 in the context of asthma-related phenotypes, although a previous study of a Japanese population demonstrated association of an IL1R2 polymorphism with aspirin hypersensitivity in asthmatic patients. 46 This same polymorphism was identified as interacting with picornavirus infection (Table IV) to modify the risk for atopic asthma in children from the CAPPS cohort.…”

Section: Discussionmentioning

confidence: 94%

Associations and interactions of genetic polymorphisms in innate immunity genes with early viral infections and susceptibility to asthma and asthma-related phenotypes

Daley

Park

et al. 2012

Journal of Allergy and Clinical Immunology

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Gene‐expression profiles in human nasal polyp tissues and identification of genetic susceptibility in aspirin‐intolerant asthma

Abstract: These results indicate that INDO and IL1R2, which were identified from gene expression analyses of nasal polyps in AIA, represent susceptibility genes for AIA.

Cited by 37 publications

References 31 publications

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

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

Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

Associations and interactions of genetic polymorphisms in innate immunity genes with early viral infections and susceptibility to asthma and asthma-related phenotypes

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