TLR3-Dependent Activation of TLR2 Endogenous Ligands via the MyD88 Signaling Pathway Augments the Innate Immune Response.
Animals
Cells, Cultured
Epithelial Cells
/ metabolism
Female
Gingiva
/ cytology
Healthy Volunteers
Humans
Immunity, Innate
Ligands
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88
/ genetics
Signal Transduction
/ genetics
Toll-Like Receptor 2
/ genetics
Toll-Like Receptor 3
/ genetics
Transfection
HMGB1
Hsp60
MyD88
TLR3
human gingival epithelial cells
pro-inflammatory cytokine
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
17 08 2020
17 08 2020
Historique:
received:
30
06
2020
revised:
12
08
2020
accepted:
12
08
2020
entrez:
23
8
2020
pubmed:
23
8
2020
medline:
20
3
2021
Statut:
epublish
Résumé
The role of the adaptor molecule MyD88 is thought to be independent of Toll-like receptor 3 (TLR3) signaling. In this report, we demonstrate a previously unknown role of MyD88 in TLR3 signaling in inducing endogenous ligands of TLR2 to elicit innate immune responses. Of the various TLR ligands examined, the TLR3-specific ligand polyinosinic:polycytidylic acid (poly I:C), significantly induced TNF production and the upregulation of other TLR transcripts, in particular, TLR2. Accordingly, TLR3 stimulation also led to a significant upregulation of endogenous TLR2 ligands mainly, HMGB1 and Hsp60. By contrast, the silencing of TLR3 significantly downregulated MyD88 and TLR2 gene expression and pro-inflammatory IL1β, TNF, and IL8 secretion. The silencing of MyD88 similarly led to the downregulation of TLR2, IL1β, TNF and IL8, thus suggesting MyD88 to somehow act downstream of TLR3. Corroborating in vitro data, Myd88
Identifiants
pubmed: 32824595
pii: cells9081910
doi: 10.3390/cells9081910
pmc: PMC7464415
pii:
doi:
Substances chimiques
Ligands
0
MYD88 protein, human
0
Myd88 protein, mouse
0
Myeloid Differentiation Factor 88
0
TLR2 protein, human
0
TLR3 protein, human
0
TLR3 protein, mouse
0
Tlr2 protein, mouse
0
Toll-Like Receptor 2
0
Toll-Like Receptor 3
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE024160
Pays : United States
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