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Role of p38 mitogen-activated protein kinase in middle ear mucosa hyperplasia during bacterial otitis media
Sean D Palacios1, Kwang Pak, Alexander Z Rivkin
1Department of Surgery/Otolaryngology, University of California-San Diego, La Jolla, 92037, USA.
Abstract:
Hyperplasia of the middle ear mucosa contributes to the sequelae of acute otitis media. Understanding the signal transduction pathways that mediate hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Endotoxin derived from bacteria involved in middle ear infection can contribute to the hyperplastic response. The p38 mitogen-activated protein kinase (MAPK) is known to be activated by endotoxin as well as cytokines and other inflammatory mediators that have been documented in otitis media. We assessed the activation of p38 in the middle ear mucosa of an in vivo rat bacterial otitis media model. Strong activity of p38 was observed 1 to 6 h after bacterial inoculation. Activity continued at a lower level for at least 7 days. The effects of p38 activation were assessed using an in vitro model of rat middle ear mucosal hyperplasia in which mucosal growth is stimulated by nontypeable Haemophilus influenzae during acute otitis media. Hyperplastic mucosal explants treated with the p38 alpha and p38 beta inhibitor SB203580 demonstrated significant inhibition of otitis media-stimulated mucosal growth. The results of this study suggest that intracellular signaling via p38 MAPK influences the hyperplastic response of the middle ear mucosa during bacterial otitis media.
Insights
Bacterial middle ear infections activate p38 mitogen-activated protein kinase (MAPK) signaling, driving mucosal hyperplasia. Inhibiting p38 MAPK significantly reduced this growth, suggesting a therapeutic target for otitis media complications.
Area of Science:
- Otolaryngology
- Molecular Biology
- Cell Signaling
Background:
- Middle ear mucosal hyperplasia is a key factor in acute otitis media sequelae.
- Bacterial endotoxins and inflammatory mediators in otitis media can trigger hyperplastic responses.
- p38 mitogen-activated protein kinase (MAPK) is a known signaling pathway activated by these inflammatory stimuli.
Purpose of the Study:
- To investigate the role of p38 MAPK activation in middle ear mucosal hyperplasia during bacterial otitis media.
- To evaluate the therapeutic potential of inhibiting p38 MAPK in this condition.
Main Methods:
- An in vivo rat model of bacterial acute otitis media was used to assess p38 MAPK activation in middle ear mucosa.
- An in vitro model of rat middle ear mucosal hyperplasia was employed, stimulated by nontypeable Haemophilus influenzae.
- The specific p38 alpha and p38 beta inhibitor, SB203580, was used to assess the effects of p38 inhibition.
Main Results:
- Strong p38 MAPK activity was detected in the middle ear mucosa 1–6 hours post-bacterial inoculation, persisting at lower levels for at least 7 days.
- Treatment with SB203580 significantly inhibited bacterial-stimulated mucosal growth in the in vitro hyperplasia model.
Conclusions:
- Intracellular signaling via p38 MAPK plays a significant role in mediating middle ear mucosal hyperplasia during bacterial otitis media.
- Targeting the p38 MAPK pathway presents a potential therapeutic strategy for managing otitis media and its associated sequelae.
