Periodontitis is a chronic inflammatory disease of the periodontium in response to a breakdown of homeostatic interactions between the subgingival microbiota and innate defense mechanisms of gingival epithelial cells. I recently found expression of six different membrane associated mucins (MAMs) in human oral epithelial tissues and show that five mucins (MUCs 1, 4, 16, 20, 21) are up-regulated after challenge of gingival cells with the commensal Streptococcus mitis and pathogen Porphyromonas gingivalis, whereas another commensal Streptococcus gordonii did not alter expression of these MAMs. I hypothesize these MAMs function in gingival epithelial homeostasis by monitoring and influencing the proximal microbiological environment, either by hindering bacterial adherence or by binding to bacteria with subsequent clearance through release of the glycosylated extracellular mucin domain. I will test this hypothesis by assessing the functions of gingival cell MAMs in bacterial adherence and invasion.
Aim 1 is to test whether MAMs released by gingival cells function as decoys by binding to oral bacterial species (S. mitis, S. gordonii or P. gingivals) and act to attenuate bacterial invasion and/or adherence.
In aim 2, I will test the novel hypothesis that S. mitis has a symbiotic relationship with epithelial cells, that by inducing the pronounced up-regulation of MAMs it provides sites for its own adherence and colonization and possibly for another commensal, S. gordonii, while limiting sites for adherence and invasion through steric hindrance of the pathogen, P. gingivalis. Results may provide new insights into host-commensal interactions that function in innate defense. An understanding of the innate defense functions of MAMs in gingival cells represents a novel and exciting area of investigation in oral biology. These studies offer to reveal new important concepts in oral epithelial homeostasis and will provide a foundation to formulate refined hypotheses of mechanisms of MAM function in future investigations.

Public Health Relevance

I find that cells of the tissues lining the oral cavity contain on their surfaces six different types of large sugar- coated proteins. I also find that cells likely mke more of these proteins when they sense certain types of good and bad bacteria found in the mouth. I intend to test whether these proteins are part of the cells normal defenses against the bad bacteria, either by hiding binding sites for bad bacteria on the cell surface, or by binding to bad bacteria and then being released from the cells to help remove these bacteria.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Postdoctoral Individual National Research Service Award (F32)
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NIDR Special Grants Review Committee (DSR)
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Frieden, Leslie A
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University of Florida
Schools of Dentistry/Oral Hygn
United States
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