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Interleukin-10 Attenuates Hypochlorous Acid-Mediated Cytotoxicity to HEI-OC1 Cochlear Cells

Overview of attention for article published in Frontiers in Cellular Neuroscience, October 2017
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Title
Interleukin-10 Attenuates Hypochlorous Acid-Mediated Cytotoxicity to HEI-OC1 Cochlear Cells
Published in
Frontiers in Cellular Neuroscience, October 2017
DOI 10.3389/fncel.2017.00314
Pubmed ID
Authors

Martin Mwangi, Sung-Hee Kil, David Phak, Hun Yi Park, David J. Lim, Raekil Park, Sung K. Moon

Abstract

Inflammatory reaction plays a crucial role in the pathophysiology of acquired hearing loss such as ototoxicity and labyrinthitis. In our earlier work, we showed the pivotal role of otic fibrocytes in cochlear inflammation and the critical involvement of proinflammatory cytokines in cisplatin ototoxicity. We also demonstrated that otic fibrocytes inhibit monocyte chemoattractant protein 1 (CCL2) upregulation in response to interleukin-10 (IL-10) via heme oxygenase 1 (HMOX1) signaling, resulting in suppression of cochlear inflammation. However, it is still unclear how IL-10 affects inflammation-mediated cochlear injury. Here we aim to determine how hypochlorous acid, a model inflammation mediator affects cochlear cell viability and how IL-10 affects hypochlorous acid-mediated cochlear cell injury. NaOCl, a sodium salt of hypochlorous acid (HOCl) was found to induce cytotoxicity of HEI-OC1 cells in a dose-dependent manner. Combination of hydrogen peroxide and myeloperoxidase augmented cisplatin cytotoxicity, and this synergism was inhibited by N-Acetyl-L-cysteine and ML-171. The rat spiral ligament cell line (RSL) appeared to upregulate the antioxidant response element (ARE) activities upon exposure to IL-10. RSL cells upregulated the expression of NRF2 (an ARE ligand) and NR0B2 in response to CoPP (a HMOX1 inducer), but not to ZnPP (a HMOX1 inhibitor). Adenovirus-mediated overexpression of NR0B2 was found to suppress CCL2 upregulation. IL-10-positive cells appeared in the mouse stria vascularis 1 day after intraperitoneal injection of lipopolysaccharide (LPS). Five days after injection, IL-10-positive cells were observed in the spiral ligament, spiral limbus, spiral ganglia, and suprastrial area, but not in the stria vascularis. IL-10R1 appeared to be expressed in the mouse organ of Corti as well as HEI-OC1 cells. HEI-OC1 cells upregulated Bcl-xL expression in response to IL-10, and IL-10 was shown to attenuate NaOCl-induced cytotoxicity. In addition, HEI-OC1 cells upregulated IL-22RA upon exposure to cisplatin, and NaOCl cytotoxicity was inhibited by IL-22. Taken together, our findings suggest that hypochlorous acid is involved in cochlear injury and that IL-10 potentially reduces cochlear injury through not only inhibition of inflammation but also enhancement of cochlear cell viability. Further studies are needed to determine immunological characteristics of intracochlear IL-10-positive cells and elucidate molecular mechanisms involved in the otoprotective activity of IL-10.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 13 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 13 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 4 31%
Student > Ph. D. Student 3 23%
Other 1 8%
Professor 1 8%
Unknown 4 31%
Readers by discipline Count As %
Medicine and Dentistry 3 23%
Neuroscience 2 15%
Psychology 1 8%
Pharmacology, Toxicology and Pharmaceutical Science 1 8%
Biochemistry, Genetics and Molecular Biology 1 8%
Other 1 8%
Unknown 4 31%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 November 2017.
All research outputs
#15,034,483
of 24,309,087 outputs
Outputs from Frontiers in Cellular Neuroscience
#2,177
of 4,515 outputs
Outputs of similar age
#177,453
of 327,260 outputs
Outputs of similar age from Frontiers in Cellular Neuroscience
#52
of 109 outputs
Altmetric has tracked 24,309,087 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,515 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one is in the 48th percentile – i.e., 48% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 327,260 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 109 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.