NOD-Like Receptor Signaling in Cholesteatoma

Background. Cholesteatoma is a destructive process of the middle ear resulting in erosion of the surrounding bony structures with consequent hearing loss, vestibular dysfunction, facial paralysis, or intracranial complications. The etiopathogenesis of cholesteatoma is controversial but is associate...

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Main Authors:	Leichtle, Anke, Klenke, Christin, Ebmeyer, Joerg, Daerr, Markus, Bruchhage, Karl-Ludwig, Hoffmann, Anna Sophie, Ryan, Allen F., Wollenberg, Barbara, Sudhoff, Holger
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398947/

id	pubmed-4398947
recordtype	oai_dc
spelling	pubmed-43989472015-04-28 NOD-Like Receptor Signaling in Cholesteatoma Leichtle, Anke Klenke, Christin Ebmeyer, Joerg Daerr, Markus Bruchhage, Karl-Ludwig Hoffmann, Anna Sophie Ryan, Allen F. Wollenberg, Barbara Sudhoff, Holger Research Article Background. Cholesteatoma is a destructive process of the middle ear resulting in erosion of the surrounding bony structures with consequent hearing loss, vestibular dysfunction, facial paralysis, or intracranial complications. The etiopathogenesis of cholesteatoma is controversial but is associated with recurrent ear infections. The role of intracellular innate immune receptors, the NOD-like receptors, and their associated signaling networks was investigated in cholesteatoma, since mutations in NOD-like receptor-related genes have been implicated in other chronic inflammatory disorders. Results. The expression of NOD2 mRNA and protein was significantly induced in cholesteatoma compared to the external auditory canal skin, mainly located in the epithelial layer of cholesteatoma. Microarray analysis showed significant upregulation for NOD2, not for NOD1, TLR2, or TLR4 in cholesteatoma. Moreover, regulation of genes in an interaction network of the NOD-adaptor molecule RIPK2 was detected. In addition to NOD2, NLRC4, and PYCARD, the downstream molecules IRAK1 and antiapoptotic regulator CFLAR showed significant upregulation, whereas SMAD3, a proapoptotic inducer, was significantly downregulated. Finally, altered regulation of inflammatory target genes of NOD signaling was detected. Conclusions. These results indicate that the interaction of innate immune signaling mediated by NLRs and their downstream target molecules is involved in the etiopathogenesis and growth of cholesteatoma. Hindawi Publishing Corporation 2015 2015-04-02 /pmc/articles/PMC4398947/ /pubmed/25922834 http://dx.doi.org/10.1155/2015/408169 Text en Copyright © 2015 Anke Leichtle et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Leichtle, Anke Klenke, Christin Ebmeyer, Joerg Daerr, Markus Bruchhage, Karl-Ludwig Hoffmann, Anna Sophie Ryan, Allen F. Wollenberg, Barbara Sudhoff, Holger
spellingShingle	Leichtle, Anke Klenke, Christin Ebmeyer, Joerg Daerr, Markus Bruchhage, Karl-Ludwig Hoffmann, Anna Sophie Ryan, Allen F. Wollenberg, Barbara Sudhoff, Holger NOD-Like Receptor Signaling in Cholesteatoma
author_facet	Leichtle, Anke Klenke, Christin Ebmeyer, Joerg Daerr, Markus Bruchhage, Karl-Ludwig Hoffmann, Anna Sophie Ryan, Allen F. Wollenberg, Barbara Sudhoff, Holger
author_sort	Leichtle, Anke
title	NOD-Like Receptor Signaling in Cholesteatoma
title_short	NOD-Like Receptor Signaling in Cholesteatoma
title_full	NOD-Like Receptor Signaling in Cholesteatoma
title_fullStr	NOD-Like Receptor Signaling in Cholesteatoma
title_full_unstemmed	NOD-Like Receptor Signaling in Cholesteatoma
title_sort	nod-like receptor signaling in cholesteatoma
description	Background. Cholesteatoma is a destructive process of the middle ear resulting in erosion of the surrounding bony structures with consequent hearing loss, vestibular dysfunction, facial paralysis, or intracranial complications. The etiopathogenesis of cholesteatoma is controversial but is associated with recurrent ear infections. The role of intracellular innate immune receptors, the NOD-like receptors, and their associated signaling networks was investigated in cholesteatoma, since mutations in NOD-like receptor-related genes have been implicated in other chronic inflammatory disorders. Results. The expression of NOD2 mRNA and protein was significantly induced in cholesteatoma compared to the external auditory canal skin, mainly located in the epithelial layer of cholesteatoma. Microarray analysis showed significant upregulation for NOD2, not for NOD1, TLR2, or TLR4 in cholesteatoma. Moreover, regulation of genes in an interaction network of the NOD-adaptor molecule RIPK2 was detected. In addition to NOD2, NLRC4, and PYCARD, the downstream molecules IRAK1 and antiapoptotic regulator CFLAR showed significant upregulation, whereas SMAD3, a proapoptotic inducer, was significantly downregulated. Finally, altered regulation of inflammatory target genes of NOD signaling was detected. Conclusions. These results indicate that the interaction of innate immune signaling mediated by NLRs and their downstream target molecules is involved in the etiopathogenesis and growth of cholesteatoma.
publisher	Hindawi Publishing Corporation
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398947/
_version_	1613212243235700736

NOD-Like Receptor Signaling in Cholesteatoma

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