title: Analysis by cDNA microarrays of altered gene expression in middle ears of rats following pneumococcal infection.
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 2.5x10(6) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Otolaryngology, University of Minnesota Otitis Media Research Center, University of Minnesota School of Medicine, 2001 Sixth Street S.E., Room 216, Minneapolis, MN 55455, USA. linxx004@tc.umn.edu
authors.forename: Jizhen
authors.initials: J
authors.lastname: Lin
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuboi
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.forename: G Scott
authors.initials: GS
authors.lastname: Giebink
authors.forename: George L
authors.initials: GL
authors.lastname: Adams
authors.forename: Youngki
authors.initials: Y
authors.lastname: Kim
mesh_terms: D000818:Animals; D001768:Blister / Q000235:genetics; D004432:Ear, Middle / Q000473:pathology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D009077:Mucins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010033:Otitis Media / Q000235:genetics* / Q000382:microbiology; D011008:Pneumococcal Infections / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000472:pathogenicity; D015854:Up-Regulation
chemical_list: D009077:Mucins; D012333:RNA, Messenger