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NTHi induction of Cxcl2 and middle ear mucosal metaplasia in mice.

ABSTRACT: Chronic otitis media (COM) develops after sustained inflammation and is characterized by secretory middle ear epithelial metaplasia and effusion, most frequently mucoid. Nontypeable Haemophilus influenzae (NTHi), the most common acute otitis media (OM) pathogen, is known to activate inflammation and mucin expression in vitro and in animal models of OM. The goals of this study were to examine histopathological and expression profiling epithelial effects of NTHi challenge in murine middle ears.In vitro and in vivo murine model of OM.Weekly transtympanic inoculation of Balb/c mice with 300 ?g/ml of NTHi lysates versus saline was performed. Histopathologic analysis was carried out at 4 weeks. Expression microarray analysis was performed at 1 and 7 days. Microarray findings were validated in independent animal samples and in a cultured murine middle ear epithelial cell (mMEEC) line.Histopathologic analyses revealed middle ear mucosal thickening after NTHi exposure. Microarray analyses of inflammatory response genes which changed significantly demonstrated that the chemokine Cxcl2 had the largest fold-change, with significantly increased expression at 1 and 7 days after NTHi injection compared to either saline or no-injection (P <0.01). Validation by real-time qPCR revealed similar significantly increased relative mRNA levels for Cxcl2. NTHi lysates were also found to significantly upregulate the transcription of Cxcl2 in mMEEC in a time- and dose-dependent manner (P <0.05).Middle ear NTHi challenge in mice leads to chronic epithelial mucosal metaplasia and overexpression of inflammatory mediators, most notably Cxcl2. This finding is parallel to NTHi-mediated pulmonary mucosal metaplasia where Cxcl2 has been identified as an important inflammatory mediator.

SUBMITTER: Preciado D

PROVIDER: S-EPMC3740030 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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NTHi induction of Cxcl2 and middle ear mucosal metaplasia in mice.

Preciado Diego D Burgett Katelyn K Ghimbovschi Svetlana S Rose Mary M

The Laryngoscope 20130401 11

<h4>Objectives/hypothesis</h4>Chronic otitis media (COM) develops after sustained inflammation and is characterized by secretory middle ear epithelial metaplasia and effusion, most frequently mucoid. Nontypeable Haemophilus influenzae (NTHi), the most common acute otitis media (OM) pathogen, is known to activate inflammation and mucin expression in vitro and in animal models of OM. The goals of this study were to examine histopathological and expression profiling epithelial effects of NTHi chall ...[more]

PMID: 23553435

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Project description:Objective: Otitis media is known to alter expression of cytokine and other genes in the mouse middle ear and inner ear. However, whole mouse genome studies of gene expression in otitis media have not previously been undertaken. Ninety-nine percent of mouse genes are shared in the human, so these studies are relevant to the human condition. Methods: To assess inflammation-driven processes in the mouse ear, gene chip analyses were conducted on mice treated with trans-tympanic heat-killed Hemophilus influenza using untreated mice as controls. Middle and inner ear tissues were separately harvested at 6 hours, RNA extracted, and samples for each treatment processed on the Affymetrix 430 2.0 Gene Chip for expression of its 34,000 genes. Results: Statistical analysis of gene expression compared to control mice showed significant alteration of gene expression in 2,355 genes, 11% of the genes tested and 8% of the mouse genome. Significant middle and inner ear upregulation (fold change >1.5, p<0.05) was seen in 1,081 and 599 genes respectively. Significant middle and inner ear downregulation (fold change <0.67, p<0.05) was seen in 978 and 287 genes respectively. While otitis media is widely believed to be an exclusively middle ear process with little impact on the inner ear, the inner ear changes noted in this study were numerous and discrete from the middle ear responses. This suggests that the inner ear does indeed respond to otitis media and that its response is a distinctive process. Numerous new genes, previously not studied, are found to be affected by inflammation in the ear. Conclusion: Whole genome analysis via gene chip allows simultaneous examination of expression of hundreds of gene families influenced by inflammation in the middle ear. Discovery of new gene families affected by inflammation may lead to new approaches to the study and treatment of otitis media. There are 8 control samples and 9 samples trans-tympanically injected with H flu 10e9 for 6 hours. Each sample is from a single animal.

Dataset Information

NTHi induction of Cxcl2 and middle ear mucosal metaplasia in mice.

Publications

NTHi induction of Cxcl2 and middle ear mucosal metaplasia in mice.

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