This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Bacterial Infections  • Genetics of Head & Neck Disease  • Middle/ External Ear Disorders  • Pediatric Otolaryngology  • Pediatrics  • Pediatrics, Other  • Genetics  • Genetic Counseling/ Testing/ Therapy  • Genetic Disorders  • Infectious Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

Joseph E. Kerschner, MD; Edward Horsey, PhD; Azad Ahmed, MD; Christy Erbe, BS; Pawjai Khampang, MS; Joseph Cioffi, PhD; Fen Ze Hu, PhD; James Christopher Post, MD, PhD; Garth D. Ehrlich, PhD

Arch Otolaryngol Head Neck Surg. 2009;135(1):33-39.

Objectives  To investigate genetic differences in middle ear mucosa (MEM) with nontypeable Haemophilus influenzae (NTHi) infection. Genetic upregulation and downregulation occurs in MEM during otitis media (OM) pathogenesis. A comprehensive assessment of these genetic differences using the techniques of complementary DNA (cDNA) library creation has not been performed.

Design  The cDNA libraries were constructed from NTHi-infected and noninfected chinchilla MEM. Random clones were picked, sequenced bidirectionally, and submitted to the National Center for Biotechnology Information (NCBI) Expressed Sequence Tags database, where they were assigned accession numbers. These numbers were used with the basic local alignment search tool (BLAST) to align clones against the nonredundant nucleotide database at NCBI.

Results  Analysis with the Web-based statistical program FatiGO identified several biological processes with significant differences in numbers of represented genes. Processes involved in immune, stress, and wound responses were more prevalent in the NTHi-infected library. S100 calcium-binding protein A9 (S100A9); secretory leukoprotease inhibitor (SLPI); β₂-microglobulin (B2M); ferritin, heavy-chain polypeptide 1 (FTH1); and S100 calcium-binding protein A8 (S100A8) were expressed at significantly higher levels in the NTHi-infected library. Calcium-binding proteins S100A9 and S100A8 serve as markers for inflammation and have antibacterial effects. Secretory leukoprotease inhibitor is an antibacterial protein that inhibits stimuli-induced MUC1, MUC2, and MUC5AC production.

Conclusions  A number of genes demonstrate changes during the pathogenesis of OM, including SLPI, which has an impact on mucin gene expression; this expression is known to be an important regulator in OM. The techniques described herein provide a framework for future investigations to more thoroughly understand molecular changes in the middle ear, which will likely be important in developing new therapeutic and intervention strategies.

Author Affiliations: Division of Pediatric Otolaryngology (Dr Kerschner) and Department of Otolaryngology and Communication Sciences (Drs Kerschner and Cioffi and Mss Erbe and Khampang), Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee; and Center for Genomic Sciences, Allegheny-Singer Research Institute, Pittsburgh, Pennsylvania (Drs Horsey, Ahmed, Hu, Post, and Ehrlich).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?