Inhibitory effects of dynorphin 3-14 on the lipopolysaccharide-induced toll-like receptor 4 signalling pathway

Rahiman, Siti Sarah Fazalul, Morgan, Michael, Gray, Paul, Shaw, Paul Nicholas and Cabot, Peter John (2017) Inhibitory effects of dynorphin 3-14 on the lipopolysaccharide-induced toll-like receptor 4 signalling pathway. Peptides, 90 48-54. doi:10.1016/j.peptides.2017.02.004


Author Rahiman, Siti Sarah Fazalul
Morgan, Michael
Gray, Paul
Shaw, Paul Nicholas
Cabot, Peter John
Title Inhibitory effects of dynorphin 3-14 on the lipopolysaccharide-induced toll-like receptor 4 signalling pathway
Journal name Peptides   Check publisher's open access policy
ISSN 1873-5169
0196-9781
Publication date 2017-04-01
Sub-type Article (original research)
DOI 10.1016/j.peptides.2017.02.004
Open Access Status Not yet assessed
Volume 90
Start page 48
End page 54
Total pages 7
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2018
Language eng
Abstract Dynorphin 1-17 (DYN 1-17) is biotransformed rapidly to a range of fragments in rodent inflamed tissue with dynorphin 3-14 (DYN 3-14) being the most stable and prevalent. DYN 1-17 has been shown previously to be involved in the regulation of inflammatory response following tissue injury, in which the biotransformation fragments of DYN 1-17 may possess similar features. This study investigated the effects of DYN 3-14 on lipopolysaccharide (LPS)-induced nuclear factor-kappaB/p65 (NF-κB/p65) nuclear translocation and the release of pro-inflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) in differentiated THP-1 cells. Treatment with DYN 3-14 (10 nM) resulted in 35% inhibition of the LPS-induced nuclear translocation of NF-κB/p65. Furthermore, DYN 3-14 modulated both IL-1β and TNF-α release; inhibiting IL-1β and paradoxically augmenting TNF-α release in a concentration-independent manner. A number of opioids have been implicated in the modulation of the toll-like receptor 4 (TLR4), highlighting the complexity of their immunomodulatory effects. To determine whether DYN 3-14 modulates TLR4, HEK-Blue™−hTLR4 cells were stimulated with LPS in the presence of DYN 3-14. DYN 3-14 (10 μM) inhibited TLR4 activation in a concentration-dependent fashion by suppressing the LPS signals around 300-fold lower than LPS-RS, a potent TLR4 antagonist. These findings indicate that DYN 3-14 is a potential TLR4 antagonist that alters cellular signaling in response to LPS and cytokine release, implicating a role for biotransformed endogenous opioid peptides in immunomodulation.
Keyword B/p65
Dynorphin
IL-1β
LPS
NF-κ
TLR4
TNF-α
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Medicine Publications
School of Pharmacy Publications
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 06 Mar 2017, 12:42:25 EST by Mr Michael Morgan on behalf of Learning and Research Services (UQ Library)