TY - JOUR
T1 - TNFA deletion alters apoptosis as well as caspase 3 and 4 expression during otitis media
AU - Ebmeyer, Joerg
AU - Leichtle, Anke
AU - Hernandez, Michelle
AU - Ebmeyer, Umay
AU - Husseman, Jacob
AU - Pak, Kwang
AU - Sudhoff, Holger
AU - Broide, David
AU - Wasserman, Stephen I.
AU - Ryan, Allen F.
PY - 2011/1/26
Y1 - 2011/1/26
N2 - Background: Tumor necrosis factor (TNFA) is the canonical member of the TNF superfamily, which plays a major role in both inflammation and apoptosis. To evaluate the role of TNFs in otitis media (OM), the most common disease of childhood, we evaluated middle ear (ME) expression of genes encoding the TNF and TNF receptor superfamilies during bacterial OM in the mouse, characterized OM in TNFA-deficient mice, and assessed apoptosis during OM in normal versus TNF-deficient MEs.Results: TNFs and TNF receptors were broadly regulated during OM, with TNFA showing the highest level of up-regulation. TNF deficient mice exhibited mucosal hyperplasia even in the absence of infection and exuberant growth of the mucosa during OM, including the formation of mucosal polyps. Mucosal recovery during OM was also delayed, in parallel with a delay in mucosal apoptosis and reduced caspase gene expression.Conclusions: The TNF and TNF receptor superfamilies mediate both inflammation and apoptosis during OM. TNF appears to be critical for the maintenance of mucosal architecture in both the normal and infected ME, since excessive accumulation of mucosal tissue is seen in TNFA-/- MEs both before and after bacterial inoculation of the ME. TNFA is also required for appropriate regulation of caspase genes.
AB - Background: Tumor necrosis factor (TNFA) is the canonical member of the TNF superfamily, which plays a major role in both inflammation and apoptosis. To evaluate the role of TNFs in otitis media (OM), the most common disease of childhood, we evaluated middle ear (ME) expression of genes encoding the TNF and TNF receptor superfamilies during bacterial OM in the mouse, characterized OM in TNFA-deficient mice, and assessed apoptosis during OM in normal versus TNF-deficient MEs.Results: TNFs and TNF receptors were broadly regulated during OM, with TNFA showing the highest level of up-regulation. TNF deficient mice exhibited mucosal hyperplasia even in the absence of infection and exuberant growth of the mucosa during OM, including the formation of mucosal polyps. Mucosal recovery during OM was also delayed, in parallel with a delay in mucosal apoptosis and reduced caspase gene expression.Conclusions: The TNF and TNF receptor superfamilies mediate both inflammation and apoptosis during OM. TNF appears to be critical for the maintenance of mucosal architecture in both the normal and infected ME, since excessive accumulation of mucosal tissue is seen in TNFA-/- MEs both before and after bacterial inoculation of the ME. TNFA is also required for appropriate regulation of caspase genes.
UR - http://www.scopus.com/inward/record.url?scp=79251543337&partnerID=8YFLogxK
U2 - 10.1186/1471-2172-12-12
DO - 10.1186/1471-2172-12-12
M3 - Journal articles
C2 - 21269505
AN - SCOPUS:79251543337
SN - 1471-2172
VL - 12
JO - BMC Immunology
JF - BMC Immunology
M1 - 12
ER -