TNFA deletion alters apoptosis as well as caspase 3 and 4 expression during otitis media

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.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.Tumor necrosis factor (TNFA, TNFSF2), formally known as TNFα, is a pleiotropic cytokine widely involved in apoptosis as well as cell proliferation, immune and inflammatory reactions. It is produced by activated macrophages and mast cells, and also by epithelial and stromal cells. TNFA is the founding member of the TNF superfamily, now composed of more than 20 members. Through interaction with their large family of cognate TNF receptors (TNFRs), TNFs can activate transcription factors such as NF-κB and c-Jun, which modulate expression of genes related to apoptosis and various other cellular responses, or via TNFR death domains which can directly stimulate cell death [1-5].Together with interleukin-1β, TNFA is considered one of the primary cytokines of middle ear (ME) inflammation [6]. In the early stage of inflammation, TNFA is produced by the ME mucosa and in the late stage also by accumulating inflammatory cells. TNFA is induced by bacterial pathogens, both Gram-positive and Gram-negative and it participates in viral otitis media (OM) [7-9]. Elevated levels of TNFA in the ME fluids of patients with OM are very common [10]. In rat and mouse models of acute OM, the expression of TNFA t