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Tympanic membrane metalloproteinase inflammatory response
Jason G Wilmoth1, Gregory S Schultz, Patrick J Antonelli
1Department of Otolaryngology, University of Florida, Gainesville, FL 32610-0264, USA.
Objective:
The goal of this study was to determine whether expression of matrix metalloproteinases (MMP) in tympanic membranes (TM) is stimulated by host tumor necrosis factor-alpha (TNF-alpha) and bacterial toxin (lipopolysaccharide, LPS), which may play a role in the pathogenesis of cholesteatoma.
Study Design:
Gerbil TMs (n = 48) were cultured in the presence of either TNF-alpha or LPS. Quantitative analysis of TNF-alpha and MMPs was performed on both the homogenized TMs and the culture media supernatant.
Results:
Levels of TNF-alpha and MMPs did not increase significantly in TMs with exposure to inflammatory mediators. TNF-alpha levels in supernatant were elevated (P < 0.007) with more concentrated LPS exposure. Supernatant levels of MMP2 were increased (P < 0.007) at most concentrations of LPS and TNF-alpha.
Conclusion:
Cultured TMs expressed MMPs in response to bacterial and host inflammatory mediators. These findings support a link between inflammation and the secretion of potentially destructive MMPs in the TM, which may contribute to the pathogenesis of cholesteatoma.
Insights
Matrix metalloproteinases (MMPs) in tympanic membranes (TM) are expressed in response to inflammatory mediators like tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS). This suggests a role for MMPs in cholesteatoma pathogenesis.
Area of Science:
- Otolaryngology
- Biochemistry
- Pathology
Background:
- Cholesteatoma pathogenesis involves complex inflammatory processes.
- Matrix metalloproteinases (MMPs) are implicated in tissue remodeling and degradation.
Purpose of the Study:
- To investigate if tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide (LPS) stimulate MMP expression in tympanic membranes (TM).
- To explore the potential role of this stimulation in cholesteatoma development.
Main Methods:
- Gerbil tympanic membranes (TMs) were cultured with TNF-alpha or LPS.
- Quantitative analysis of TNF-alpha and MMPs was conducted on homogenized TMs and culture supernatants.
Main Results:
- TMs cultured with inflammatory mediators showed MMP expression.
- Supernatant levels of MMP2 increased with exposure to LPS and TNF-alpha.
- TNF-alpha levels in the supernatant also elevated with LPS exposure.
Conclusions:
- Cultured TMs express MMPs when exposed to bacterial and host inflammatory mediators.
- These findings support a link between inflammation and MMP secretion in the TM.
- This MMP secretion may contribute to the pathogenesis of cholesteatoma.
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