☆ 3.9 Article Proceedings Paper

Gene Expression Differences in Infected and Noninfected Middle Ear Complementary DNA Libraries

ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY (2009)

Journal

ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY

Volume 135, Issue 1, Pages 33-39

Publisher

AMER MEDICAL ASSOC

DOI: 10.1001/archoto.2008.513

Keywords

Funding

NIDCD NIH HHS [R01 DC004173-08, R01 DC004173, R01 DC007903, R01 DC002148, DC007903, R01 DC007903-02, K08 DC000192, K08DC00192, DC02148, DC04173, R01 DC005659, R01 DC005659-05, R01 DC002148-16, K08 DC000192-05, DC05659] Funding Source: Medline
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS [R01DC002148, R01DC007903, R01DC004173, R01DC005659, K08DC000192] Funding Source: NIH RePORTER

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Abstract

Objectives: To investigate genetic differences in middle ear mucosa (MEM) with nontypeable Haemophilus influenzae (NTHi) infection. Genetic upregulation and downregulation occurs inMEMduring 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); beta(2)-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.

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Differences between infected and noninfected synovial fluid

P. Akhbari, M. K. Jaggard, C. L. Boulange, U. Vaghela, G. Graca, R. Bhattacharya, J. C. Lindon, H. R. T. Williams, C. M. Gupte

Summary: The study used nuclear magnetic resonance spectroscopy to identify small molecule differences between infected and noninfected human synovial fluid. A total of 16 metabolites were found in significantly different concentrations between the two groups, with potential as new diagnostic biomarkers for infected synovial fluid.

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