El-Kady, Mona Anwar M. H.
(2010)
INTERFERON-ALPHA SIGNALING PATHWAY IN THE SENSORY AUDITORY NEUROEPITHELIAL CELLS.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
The current study investigated the effect of interferon-á (IFN-á) on the cochlear cell line to shed light on the mechanisms by which interferon alpha may affect hearing. HEI-OC1 cell line and real time-PCR were used to determine the expression of those genes that might be involved in these mechanisms. Dose- (20, 40, & 80 U/ml) and time-dependent experiment-1 did not show significant alteration in gene expression associated with the stimulations of the IFN-á receptors. Therefore, a second experiment was planned. A 3 X 4 factorial design, consisting of three treatment conditions (0, 200 & 2000U/ml) and four time-points (6, 12, 24 & 48 Hrs), was employed. The results of experiment-2 revealed that significant differential expression of inflammatory genes, immune response genes and apoptotic genes is found in a dose- and time-dependent manner. This outcome indicates that IFN-á treatment led to initiation of an inflammatory response, an immune response and apoptosis of the cochlear cells, which was confirmed by a reduction in cell viability. The immune response was the most pronounced response; whereas inflammatory the apoptotic responses were transient. Therefore, the current in-vitro study indicates that the inflammatory response, the immune response and apoptosis might be the underlying mechanisms involved in the hearing impairment previously reported in patients under IFN-á therapy. These results imply that pre-treatment hearing evaluation as well as close monitoring of hearing function in patients undergoing long-term high-dose of IFN-á therapy are necessary to avoid or to minimize its adverse effect on hearing. The results also indicate that there is a need for further investigation of other markers that might be involved in signaling pathways of IFN-á, including markers for intrinsic pathway of apoptosis and antiapoptotic markers as well as markers for necrosis. This information might open an avenue for therapeutic intervention that can protect the inner ear from the ototoxic effect of some medications in general and IFN-á in particular and treat some immune-mediated inner ear disorders. In addition, this information might help in identifying novel diagnostic markers for vulnerability, severity, and outcomes of any cochlear pathology.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| El-Kady, Mona Anwar M. H. | melkady@pitt.edu | MELKADY | |
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| ETD Committee: |
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| Date: |
19 August 2010 |
| Date Type: |
Completion |
| Defense Date: |
30 July 2009 |
| Approval Date: |
19 August 2010 |
| Submission Date: |
26 July 2010 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Health and Rehabilitation Sciences > Communication Science and Disorders |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
immune response; inner ear; interferon-alpha; ototoxicity; apoptosis; cochlear cell line |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-07262010-174213/, etd-07262010-174213 |
| Date Deposited: |
10 Nov 2011 19:54 |
| Last Modified: |
19 Dec 2016 14:36 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/8632 |
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