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Immunomodulatory response of the middle ear mucosa in otitis media and its therapeutic approaches
18 April 2018 (online)
A major feature of the pathogenesis in otitis media, the most common disease in childhood, is an uncontrolled hyperplasia of the middle ear mucosa. Activation of innate immune receptors during the inflammatory process leads to the activation of intracellular transcription factors (NF-kB), which regulate both inflammatory response and cell tissue growth. We investigated these leading signaling pathways in otitis media in patient tissue and in "Human Middle Ear Epithelial Cell (HMEEC)" lines for therapeutic immunomodulation.
Middle ear mucosa and healthy mucosa were removed during surgery procedures. Gen- and protein expression of the TLR-/NLR-related signal molecules was evaluated using qPCR, IHC, Elisa and Western blot. TUNEL staining and in situ apoptosis detection kit determined the apoptotic rate. The influence of the otitis media infection of different immunomodulating molecules (TNFα, MDP, Tri-DAP, SB203580, CHX) in HMEEC and NOD-overexpressed cells was examined after stimulation/inhibition on growth behavior and gene expression.
According to clinically and immunohistologically apparent uncontrolled persisting mucosal hyperplasia of the middle ear mucosa in chronic otitis media, a dysregulated gene and protein expression of inflammatory and apoptotic genes, such as TNF, CCL3, Casp3 and cleaved Casp3, could be detected. These molecules were regulated in the chronic middle ear inflammation of patients and after specific stimulation in the HMEECs and are thus suitable as possible immunological therapy approaches.
Uncontrolled middle-ear mucosal hyperplasia is triggered by TLRs/NLRs immunoreceptors downstream inflammatory and apoptotic molecules.