Glucocorticoid-stimulated, transcription-independent release of annexin A1 by cochlear Hensen cells

Authors

  • F Kalinec,

    Corresponding author
    1. Division of Cell Biology and Genetics, House Ear Institute, Los Angeles, CA, USA,
    2. Department of Cell & Neurobiology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA,
    3. Department of Otolaryngology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA,
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  • P Webster,

    1. Division of Cell Biology and Genetics, House Ear Institute, Los Angeles, CA, USA,
    2. Department of Otolaryngology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA,
    3. Ahmanson Advanced EM and Imaging Center, House Ear Institute, Los Angeles, CA, USA, and
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  • A Maricle,

    1. Division of Cell Biology and Genetics, House Ear Institute, Los Angeles, CA, USA,
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  • D Guerrero,

    1. Division of Cell Biology and Genetics, House Ear Institute, Los Angeles, CA, USA,
    2. Ahmanson Advanced EM and Imaging Center, House Ear Institute, Los Angeles, CA, USA, and
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  • DN Chakravarti,

    1. Keck Graduate Institute of Applied Life Sciences, The Claremont Colleges, Claremont, CA, USA
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  • B Chakravarti,

    1. Keck Graduate Institute of Applied Life Sciences, The Claremont Colleges, Claremont, CA, USA
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  • R Gellibolian,

    1. Division of Cell Biology and Genetics, House Ear Institute, Los Angeles, CA, USA,
    2. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA,
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  • G Kalinec

    1. Division of Cell Biology and Genetics, House Ear Institute, Los Angeles, CA, USA,
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Federico Kalinec, House Ear Institute, 2100 W. 3rs Street, Los Angeles, CA 90057, USA. E-mail: fkalinec@hei.org

Abstract

Background and purpose:  The current clinical strategy to protect the auditory organ against inflammatory damage by migrating leukocytes is the local delivery of glucocorticoids. However, the mechanism by which glucocorticoids confer this protection remains unknown. Therefore, we investigated the cellular and molecular targets of glucocorticoids in the cochlea that could be involved in preventing leukocyte migration.

Experimental approach:  We used microscopy as well as immunocytochemical and microfluidic techniques to elucidate the effect of dexamethasone, hydrocortisone and prednisolone on the cellular and intracellular distribution of annexin A1 (ANXA1) – a glucocorticoid target known to inhibit leukocyte migration by receptor-mediated signalling – in the cochlea and isolated cochlear cells of guinea pigs.

Key results:  All the cells lining the scala media – the cochlear compartment containing the auditory organ – express ANXA1 and the ANXA1 receptor FPR2/ALX is present in the scala media, as well as in other cochlear ducts. The majority of ANXA1 in the scala media is stored inside lipid droplets within cochlear Hensen cells. Glucocorticoids activate a myosin IIC-mediated mechanism that drives ANXA1 from the lipid droplets to the apical region of the Hensen cells, where ANXA1 is released to the external milieu by a process involving ABC transporters.

Conclusions and implications:  These findings suggest that ANXA1 could be a major mediator of the anti-inflammatory effects of glucocorticoids in the cochlea and identify new molecular targets for prevention of sudden sensorineural hearing loss.

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