Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes
Joint Authors
Mielcarska, Matylda B.
Bossowska-Nowicka, Magdalena
Gregorczyk-Zboroch, Karolina P.
Wyżewski, Zbigniew
Szulc-Dąbrowska, Lidia
Gieryńska, Małgorzata
Toka, Felix N.
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-21, 21 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-04
Country of Publication
Egypt
No. of Pages
21
Main Subjects
Abstract EN
Toll-like receptors (TLRs) sense the presence of pathogen-associated molecular patterns.
Nevertheless, the mechanisms modulating TLR-triggered innate immune responses are not yet fully understood.
Complex regulatory systems exist to appropriately direct immune responses against foreign or self-nucleic acids, and a critical role of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), endosomal sorting complex required for transportation-0 (ESCRT-0) subunit, has recently been implicated in the endolysosomal transportation of TLR7 and TLR9.
We investigated the involvement of Syk, Hrs, and STAM in the regulation of the TLR3 signaling pathway in a murine astrocyte cell line C8-D1A following cell stimulation with a viral dsRNA mimetic.
Our data uncover a relationship between TLR3 and ESCRT-0, point out Syk as dsRNA-activated kinase, and suggest the role for Syk in mediating TLR3 signaling in murine astrocytes.
We show molecular events that occur shortly after dsRNA stimulation of astrocytes and result in Syk Tyr-342 phosphorylation.
Further, TLR3 undergoes proteolytic processing; the resulting TLR3 N-terminal form interacts with Hrs.
The knockdown of Syk and Hrs enhances TLR3-mediated antiviral response in the form of IFN-β, IL-6, and CXCL8 secretion.
Understanding the role of Syk and Hrs in TLR3 immune responses is of high importance since activation and precise execution of the TLR3 signaling pathway in the brain seem to be particularly significant in mounting an effective antiviral defense.
Infection of the brain with herpes simplex type 1 virus may increase the secretion of amyloid-β by neurons and astrocytes and be a causal factor in degenerative diseases such as Alzheimer’s disease.
Errors in TLR3 signaling, especially related to the precise regulation of the receptor transportation and degradation, need careful observation as they may disclose foundations to identify novel or sustain known therapeutic targets.
American Psychological Association (APA)
Mielcarska, Matylda B.& Bossowska-Nowicka, Magdalena& Gregorczyk-Zboroch, Karolina P.& Wyżewski, Zbigniew& Szulc-Dąbrowska, Lidia& Gieryńska, Małgorzata…[et al.]. 2019. Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-21.
https://search.emarefa.net/detail/BIM-1204920
Modern Language Association (MLA)
Mielcarska, Matylda B.…[et al.]. Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-21.
https://search.emarefa.net/detail/BIM-1204920
American Medical Association (AMA)
Mielcarska, Matylda B.& Bossowska-Nowicka, Magdalena& Gregorczyk-Zboroch, Karolina P.& Wyżewski, Zbigniew& Szulc-Dąbrowska, Lidia& Gieryńska, Małgorzata…[et al.]. Syk and Hrs Regulate TLR3-Mediated Antiviral Response in Murine Astrocytes. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-21.
https://search.emarefa.net/detail/BIM-1204920
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204920