Proteomic Networks of MUC5B Infectious/Inflammatory Induction in Otitis Media

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Key Personnel

  • Diego Preciado MD, PhD
  • Stephanie Val, PhD
  • Marian Poley
  • Mary Rose, PhD
  • Kristy Brown, PhD
  • Yetrib Hathout, PhD

Otitis media (OM), the most prevalent chronic childhood disorder, is associated with staggering public healthcare costs.  It is a disease of the middle ear space characterized by acute infectious injury and inflammation, acute OM (AOM), progressing to chronic epithelial mucoid fluid secretion, i.e., chronic OM (COM). The OM continuum from acute to chronic is triggered by infectious or noxious stimuli that result in thickening of middle ear epithelia (MEE) and leads to self-sustaining chronic inflammation and mucous hypersecretion. This, in turn, often leads to medical treatment failure, and the placement of surgical tympanostomy tubes – the most common surgical procedure of children. In published and preliminary data, we have begun to characterize the molecular progression of OM events. We have recently shown that the hyperviscous mucus in COM is characterized by an overabundance of MUC5B mucin, a major airway secreted mucin. Through a gene expression profiling approach in a mouse model of acute OM based on middle ear inoculation of  Non-typeable Hemophilus Influenza (NTHi) (currently the most common human AOM pathogen), we identified the pro-inflammatory cytokine Cxcl2 as markedly and acutely upregulated. In this project we aim to use a proteomic and cytokine secretome profiling approach to determine the in vitro effects of NTHi on a middle ear epithelial pro-inflammatory response, gaining important information that would complement our preliminary in vivo data. Our findings should result in a better understanding of pathways in OM pathophysiology and are likely to reveal novel molecular therapeutic targets that when modulated may help abate progression of AOM to COM.