Inflammatory signals increase Fas ligand expression by inner ear cells

Bodmer, Daniel; Brors, Dominik; Pak, Kwang; Keithley, Elizabeth M.; Mullen, Lina; Ryan, Allen F.; Gloddek, B.

doi:10.1016/s0165-5728(02)00143-1

Cited by 24 publications

(22 citation statements)

References 37 publications

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“…Moreover, there was no increase in FasL transcripts and/or mRNA stability in the OC after IFN-Á stimulation. This result suggests that the increases in FasL that we previously observed on cochlear cells exposed to inflammatory stimulation [Bodmer et al, 2002] are not related to changes in gene transcription. It further suggests the possible presence of preformed FasL in normal cochlear cells, protein that is sequestered from FACS and standard cytochemical analysis.…”

Section: Discussionsupporting

confidence: 62%

“…In our previous study [Bodmer et al, 2002], FasL was observed on supporting cells in the OC of sections from animals undergoing a cochlear secondary immune response. No labeling was observed in hair cells.…”

Section: Discussionmentioning

confidence: 78%

“…Therefore, it is possible that FasL transcription occurred prior to or after the period tested. However, we showed in a time course study using FACS analysis that IFN-Á-stimulated FasL appeared on the cell surface after 6 h of stimulation, with maximal surface expression observed after 48 h of stimulation [Bodmer et al, 2002]. In this prior study, we stimulated the OC every 12 h with IFN-Á.…”

Section: Discussionmentioning

confidence: 98%

“…Recently, we have demonstrated by FACS analysis and immunohistochemistry that FasL on the surface of cochlear cells increases after stimulation with Á-interferon (IFN-Á) or after the induction of a sterile labyrinthitis [Bodmer et al, 2002]. It may be involved in the defense of inner ear tissue from inflammation and immunity, as has been suggested for the anterior chamber of the eye [Griffith et al, 1996].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Fas Ligand Expression in the Organ of Corti

Bodmer¹,

Brors

Bodmer

et al. 2003

Audiol Neurotol

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“…The central nervous system, and the inner ear by extension, were originally thought to be immunoprivileged sites due to the presence of the blood-brain and the blood-labyrinthine barriers, respectively [Bodmer et al, 2002]. In 1958, Lehnhardt was the first to contradict the 'immunoprivileged site' theory about the inner ear.…”

Section: Introductionmentioning

confidence: 99%

The Expression of TNFα, IL-6, IL-2 and IL-8 in the Serum of Patients with Idiopathic Sudden Sensorineural Hearing Loss: Possible Prognostic Factors of Response to Corticosteroid Treatment

Tsinaslanidou¹,

Tsaligopoulos

Angouridakis³

et al. 2016

Audiol Neurotol Extra

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Introduction: Idiopathic sudden sensorineural hearing loss (ISSNHL) remains one of the major unsolved otologic emergencies. A viral infection, a systemic inflammatory disorder, as well as physical, mental and metabolic stress can trigger an innate immune response in the inner ear resulting in ISSNHL. Proinflammatory cytokines play a central role in this cochlear immunological cascade. Objective: To examine the expression of proinflammatory cytokines in the serum of patients with ISSNHL in correlation with the therapeutic outcome of intravenous administration of corticosteroids. Method: Forty-three patients primarily diagnosed with ISSNHL underwent intravenous corticosteroid treatment for 8 days. The expression of tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), interleukin-2 (IL-2) and interleukin-8 (IL-8) was detected with the use of enzyme-linked immunosorbent assay in serum specimens on the 1st and 8th day of treatment and it was correlated with the treatment outcome. Results: TNFα reduction and IL-6 increase strongly correlate with a good therapeutic result [χ²(2) = 13.12, p = 0.001 and χ²(2) = 16.78, p = 0.0001]. IL-8 increase reflects negatively on the outcome, however, not in a statistically significant way. No association was established between IL-2 variations and the therapeutic outcome. Conclusions: TNFα and IL-6 can be used as prognostic factors for the treatment outcome, whereas the prognostic value of IL-8 requires further statistical confirmation.

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Up‐regulation of activated macrophages in response to degeneration in the taste system: Effects of dietary sodium restriction

McCluskey

2004

J of Comparative Neurology

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Dietary sodium restriction combined with unilateral chorda tympani nerve section leads to a rapid and specific decrease in neurophysiological taste responses to sodium in the contralateral, intact chorda tympani (Hill and Phillips [1994] J. Neurosci. 14:2904-2910). Previous work demonstrated that dietary sodium restriction may induce these early functional deficits by inhibiting immune activity after denervation (Phillips and Hill [1996] Am. J. Physiol. 271:R857-R862). However, little is known about the leukocyte response to denervation of taste buds in fungiform papillae. In the current study, it was hypothesized that T cells and macrophages are increased in the tongue after unilateral denervation in control-fed but not sodium-restricted animals. Adult, specified pathogen-free rats received unilateral chorda tympani nerve section or sham section followed by dietary sodium restriction or maintenance on control diet. At day 1, 2, 5, 7, or 50 postsectioning, immunostaining was used to detect the percentage of staining for activated macrophages, the number of alpha beta T cells, and the number of delta gamma epithelial T cells in the tongue. The number of lingual T cells did not significantly differ between treatment groups following denervation. However, there was a dramatic bilateral increase in ED1(+) staining for activated macrophages in control-fed rats that peaked at day 2 postsectioning. In contrast, sodium-restricted rats did not show an increase in activated macrophages above baseline at any time postsectioning. Further analysis of extralingual macrophages indicated that the deficit in immune activity in sodium-restricted rats is localized to the tongue and is not widespread. A model for immune modulation of taste receptor cell function is proposed based on these novel findings.

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Inflammatory signals increase Fas ligand expression by inner ear cells

Cited by 24 publications

References 37 publications

Fas Ligand Expression in the Organ of Corti

Fas Ligand Expression in the Organ of Corti

The Expression of TNFα, IL-6, IL-2 and IL-8 in the Serum of Patients with Idiopathic Sudden Sensorineural Hearing Loss: Possible Prognostic Factors of Response to Corticosteroid Treatment

Up‐regulation of activated macrophages in response to degeneration in the taste system: Effects of dietary sodium restriction

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