Autoimmune disease and cochlear pathology in the C3H/lpr strain mouse

Trune, Dennis R.; Craven, James P; Morton, Jane I.; Mitchell, Curt

doi:10.1016/0378-5955(89)90128-7

Cited by 51 publications

(32 citation statements)

References 51 publications

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“…This may be related to autoimmunity since this mouse shows progressive accumulation of autoreactive Tlymphocytes. However, the most striking inner ear pathology of the Fas mutant mouse is found in the stria vascularis, with progressive hydrops and degeneration of strial cells in the absence of leukocyte infiltration of the stria (Trune et al, 1989;Ruckenstein et al, 1999). These data provide evidence that the Fas-FasL system plays a role in the inner ear, but the nature of this role remains obscure.…”

Section: Discussionmentioning

confidence: 87%

“…The inner ear appears to have evolved mechanisms, such as the blood -labyrinthine barrier, which limit immune responses and minimize autoimmunity, in order to prevent damage to the sensitive sensory cells and neurons. Mice deficient in Fas exhibit hearing loss that has been attributed to autoimmune processes (Trune et al, 1989;Ruckenstein et al, 1999). Therefore, it is possible, that FasL participates in the regulation of immunity in the inner ear.…”

Section: Introductionmentioning

confidence: 99%

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Inflammatory signals increase Fas ligand expression by inner ear cells

Bodmer

Brors²,

Pak³

et al. 2002

Journal of Neuroimmunology

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There is considerable evidence that hearing and vestibular function can be influenced by immune processes. The inner ear has evolved mechanisms, such as the blood-labyrinthine barrier that limit immune responses and autoimmune processes to reduce the potential for damage to cochlear cells. Recently, expression of Fas ligand (FasL) in some non-lymphoid tissue, as in the anterior chamber of the eye, has been hypothesized to play a role in protection of sensitive organs from activated T-cells. We show that under resting conditions, cochlear cells express little or no FasL. However, after exposure to interferon-gamma in vitro, FasL is induced in many neonatal cochlear cells. In addition, we show that FasL is upregulated in adult cochlear cells after induction of a sterile labyrinthitis in vivo. The induction of FasL by inflammation may serve to limit cochlear immune responses, and to protect sensorineural tissue from immune and autoimmune damage. AbstractThere is considerable evidence that hearing and vestibular function can be influenced by immune processes. The inner ear has evolved mechanisms, such as the blood -labyrinthine barrier that limit immune responses and autoimmune processes to reduce the potential for damage to cochlear cells. Recently, expression of Fas ligand (FasL) in some non-lymphoid tissue, as in the anterior chamber of the eye, has been hypothesized to play a role in protection of sensitive organs from activated T-cells. We show that under resting conditions, cochlear cells express little or no FasL. However, after exposure to interferon-g in vitro, FasL is induced in many neonatal cochlear cells. In addition, we show that FasL is upregulated in adult cochlear cells after induction of a sterile labyrinthitis in vivo. The induction of FasL by inflammation may serve to limit cochlear immune responses, and to protect sensorineural tissue from immune and autoimmune damage. D

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Inflammatory signals increase Fas ligand expression by inner ear cells

Bodmer

Brors²,

Pak³

et al. 2002

Journal of Neuroimmunology

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“…In the OC, expression of FasL on supporting cells could serve to protect the hair cells, which are surrounded by supporting cells. Relevant to this hypothesis, mice deficient in Fas have been proposed to be a model for autoimmune inner ear damage [Trune et al, 1989]. Alternatively, FasL could participate in the death of OC cells in response to stress.…”

Section: Discussionmentioning

confidence: 99%

Fas Ligand Expression in the Organ of Corti

Bodmer¹,

Brors

Bodmer

et al. 2003

Audiol Neurotol

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We have previously demonstrated by FACS analysis and histochemistry that Fas ligand (FasL) increases on cochlear cell surfaces after immune response or stimulation with γ-interferon (IFN-γ). To determine whether the appearance of FasL on cochlear cell membranes is related to gene expression or to posttranslational events, cochlear cells were treated with IFN-γ. They were evaluated for FasL gene expression by real-time PCR and for FasL protein localization by confocal microscopy of permeabilized and immunolabeled cells. Real-time PCR analysis of cDNAs generated from unstimulated or IFN-γ-stimulated organ of Corti demonstrated no change in the transcription of the gene encoding FasL. In contrast, confocal microscopy revealed dramatic changes in the cellular distribution of FasL, consistent with movement from the endoplasmic reticulum to the cytoplasm and cell membrane. The results suggest that recruitment of preformed FasL from intracellular compartments, rather than its biosynthesis, is responsible for the increase in FasL on the cell surface following IFN-γ stimulation. This is similar to the response of cytotoxic T lymphocytes in which gene expression is not involved in FasL surface appearance. Presumably, the use of preformed FasL increases the rapidity of this response. FasL localization to the membrane may be involved in protecting the inner ear from autoimmunity or inflammation. Alternatively it may be related to cochlear cell death in response to inflammatory stress.

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“…Both cellular and humoral mechanisms have been implicated (Barna and Hughes, 1988). A study of the C3H/lpr murine model of lupus has shown that there is degeneration of the stria vascularis (Trumer et al, 1989). A temporal bone study in three cases of SLE revealed fibrosis and new bone formation in the internal ear (Yoonetal, 1989).…”

Section: Discussionmentioning

confidence: 99%

Audiovestibular manifestations of the antiphospholipid syndrome

1994

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We report on two patients who have high titres of antiphospholipid antibodies, both of whom had acute audiovestibular failure. One of the patients had systemic lupus erythematosus. The other patient had primary antiphospholipid syndrome: audiovestibular symptoms have not been reported in this condition. The occurrence of acute audiovestibular failure in the primary antiphospholipid syndrome raises the question as to whether patients presenting with acute deafness or vestibular disturbance should be screened for the presence of anticardiolipin antibodies.

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Autoimmune disease and cochlear pathology in the C3H/lpr strain mouse

Cited by 51 publications

References 51 publications

Inflammatory signals increase Fas ligand expression by inner ear cells

Inflammatory signals increase Fas ligand expression by inner ear cells

Fas Ligand Expression in the Organ of Corti

Audiovestibular manifestations of the antiphospholipid syndrome

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