Assessment of the occurrence and function of microbial HMGB1 in the pathogenesis of chronic otitis media with cholesteatoma.

Chronic otitis media with cholesteatoma is still a major therapeutic problem. During the development of cholesteatoma, the cells of the keratinized epithelium from the external auditory canal to the middle ear cavity "crawl" and proliferate, causing chronic inflammation as a result of the activation of the immune system. As a result, the structures of the middle and inner ear are destroyed, leading to hearing loss, paralysis of the facial nerve, balance disorders (vestibular dysfunction), as well as a risk of intra-temporal and intracranial complications.The reasons for the formation and development of cholesteatoma are not fully understood. Surgical treatment is the treatment of choice. In our previous studies, we have shown a significant role of innate immunity in the development of acquired middle ear cholesteatoma. Our preliminary studies showed the presence of the HMGB1 protein and its RAGE receptor, as well as the presence of Toll-like receptors in the cholesteatoma microenvironment. Currently, more and more data indicate the key role of extracellular vesicles (EV) in the pathogenesis of chronic inflammation, because EVs act as carriers of various proteins, including pro-inflammatory modulating the activities of other cells. Taking into account the results of our preliminary studies, we hypothesize that by releasing HMGB1-containing microvesicles from the microenvironment of cholesteatoma, which is also spread systemically through the circulatory system, local and general inflammation occurs. Due to the fact that microvesicles can be collected by endocytosis by cells of the immune system, such as macrophages, but also by other cells (fibroblasts, vascular endothelium), we want to assess the direct impact of microvesicle HMGB1 (EV-HMGB1) on these cells in research in vitro and ex vivo. We also assume that the assessment of the number of microvesicles and the level of HMGB1 in the serum may be a marker of inflammation and correlate with the clinical advancement of cholesteatoma or its recurrence.