The role of Fas-mediated apoptosis in otitis media: observations in the lpr/lpr mouse.
Apoptosis, or programmed cell death, is a critical regulatory mechanism involved in the function, homeostasis and stimulus response of many organ systems. In the middle ear, apoptosis could participate in mucosal remodeling or leukocyte clearance during otitis media (OM). Fas is a death receptor that can contribute to apoptosis in a variety of cell types. To assess the role of Fas signaling in OM, we probed for expression of Fas and Fas ligand (FasL) by polymerase chain reaction (PCR) during bacterial OM in the rat. In addition, we assessed the response of the middle ear to endotoxin, an inflammatory bacterial product that has been used as a model for otitis media in the mouse, in normal and Fas deficient mice. We saw evidence of increased expression of Fas and Fas ligand during bacterial OM. Moreover, the intensity of the mucosal response to endotoxin was significantly greater and the resolution of the response was prolonged in Fas deficient mice. Prolonged resolution of mucosal hyperplasia may reflect reduced apoptosis of the hyperplastic mucosal cells. Elucidation of the pathways that regulate the mucosal hyperplastic response during otitis media brings us closer to manipulating them in the interest of reducing the chronic complications of this disease.
Department of Surgery, Division Otolaryngology, UCSD School of Medicine and VA Medical Center, 9500 Gilman Drive number 0666, Fir Building, Room 106, La Jolla, CA 92093, USA.
Alexander Z
AZ
Rivkin
Sean D
SD
Palacios
Kwang
K
Pak
Thecla
T
Bennett
Allen F
AF
Ryan
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008808:Mice, Inbred CBA; D019463:Mice, Inbred MRL lpr; D010033:Otitis Media / Q000235:genetics / Q000473:pathology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000502:physiology; D019014:fas Receptor
D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D048069:Tumor Necrosis Factors; D019014:fas Receptor; D004247:DNA