Analysis by cDNA microarrays of altered gene expression in middle ears of rats following pneumococcal infection

Jizhen Lin, Yasuhiro Tsuboi, Wei Pan, G. Scott Giebink, George L. Adams, Youngki Kim

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Objective: Streptococcus pneumoniae is the most common pathogen in otitis media. Infection of the middle ear with S. pneumoniae potentiates development of thick effusion in the middle ear which frequently causes hearing loss and communication disorders in children. What has changed immediately in the middle ear cleft following pneumococcal infection is extensively studied and characterized but what has changed ever after remains elusive. The purpose of this study is to explore the cellular and molecular basis that remains on a longer time after acute pneucmococcal middle ear infection and potentiates development of thick effusion in the middle ear. Methods: 12 rats were intrabullarly inoculated with pneumococcus at 2.5 × 106 CFU/ear and profiles of gene expression in the middle ear were examined by cDNA microarrays in combination with reverse transcription-polymer chain reaction (RT-PCR) 6 weeks after infection while the morphologic changes in middle ear were simultaneously characterized by histopathologic techniques. Twelve rats receiving phosphate-buffered saline (PBS) served as controls. Results: it demonstrated that pneumococcus infected ears had the expression of the following genes at a high level compared to the controls: mitogenic signaling proteins (mitogen-activated protein kinase [MEK1 and MEK2], helix-loop-helix transcriptional regulators (Id3 and Id1), ion channels (sodium channel beta 1 and sodium channel 2), and mucin glycoproteins (Muc2 and Muc5). The morphology demonstrated a thickened mucosa and submucosa with increased expression of macroglycoconjugates compared to the controls. Conclusion: the expression of several genes remains high even after the acute episode of pneumococcal otitis media has been resolved. The up-regulated expression of these genes may serve as the basis for the development of thick effusion and mucous cell metaplasia/hyperplasia once it is complicated with other factors such as dysfunction of the Eustachian tube.

Original languageEnglish (US)
Pages (from-to)203-211
Number of pages9
JournalInternational Journal of Pediatric Otorhinolaryngology
Volume65
Issue number3
DOIs
StatePublished - Sep 24 2002

Bibliographical note

Funding Information:
The authors would like to thank Ms. Phoebe McCullough for the editorial assistance in the preparation of the manuscript. Supported by NIH grant no. R01 DC03433 (Microarray Administrative Suppplement) from the National Institute of Deafness and Other Communication Disorders, the National Organization for Hearing Research, the Lions Hearing Foundation, and the Vikings’ Children Fund.

Keywords

  • Altered gene expression
  • Pneumococcal infection
  • cDNA microarrays

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