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Upregulated TRPC5 plays an important role in development of nasal polyps by activating eosinophilic inflammation and NF-?B signaling pathways.

ABSTRACT: The pathophysiology of nasal polyps (NP) remains unclear, however, several ion channels may participate. Whether transient receptor potential canonical (TRPC) channel play a role in NP remains unknown. We investigated expression of TRPC, eosinophil infiltration, IL-6, and NF-?B in 58 patients with NP and 35 control subjects using hematoxylin-eosin (HE) staining, immunohistochemistry, real-time fluorescence quantitative reverse transcription PCR (real-time RT-PCR), Western blotting, and calcium imaging. Compared with normal nasal mucosa, TRPC5 mRNA and protein expression increased in NP. Eosinophil counts, IL-6 expression, and phosphorylation levels of NF-?B were higher in NP than in normal mucosa. TRPC5 expression was positively correlated with eosinophils, IL-6, and phosphorylation levels of NF-?B. Blocking of TRPC5 channel decreased store-operated calcium influx, IL-6 expression, and phosphorylation levels of NF-?B in blood eosinophils from patients with NP. In conclusion, TRPC5 was upregulated in NP and played an important role in development of NP by activating eosinophilic inflammation and NF-?B signal pathways.

SUBMITTER: Fu Z

PROVIDER: S-EPMC6958183 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Upregulated TRPC5 plays an important role in development of nasal polyps by activating eosinophilic inflammation and NF-κB signaling pathways.

Fu Zhijie Z Gu Lintao L Li Na N Ma Zhiyong Z Ling Mingying M Wang Yuanyuan Y

International journal of clinical and experimental pathology 20180401 4

The pathophysiology of nasal polyps (NP) remains unclear, however, several ion channels may participate. Whether transient receptor potential canonical (TRPC) channel play a role in NP remains unknown. We investigated expression of TRPC, eosinophil infiltration, IL-6, and NF-κB in 58 patients with NP and 35 control subjects using hematoxylin-eosin (HE) staining, immunohistochemistry, real-time fluorescence quantitative reverse transcription PCR (real-time RT-PCR), Western blotting, and calcium i ...[more]

PMID: 31938299

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Project description:BackgroundRecent 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.MethodsPatients 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).ResultsMicroarray 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.ConclusionThis 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.

Dataset Information

Upregulated TRPC5 plays an important role in development of nasal polyps by activating eosinophilic inflammation and NF-?B signaling pathways.

Publications

Upregulated TRPC5 plays an important role in development of nasal polyps by activating eosinophilic inflammation and NF-κB signaling pathways.

Similar Datasets

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