Molecular Mechanism of the Anti-Inflammatory Action of Heparin.
Int J Mol Sci
; 22(19)2021 Oct 03.
Article
in English
| MEDLINE | ID: covidwho-1444234
ABSTRACT
Our objective is to reveal the molecular mechanism of the anti-inflammatory action of low-molecular-weight heparin (LMWH) based on its influence on the activity of two key cytokines, IFNγ and IL-6. The mechanism of heparin binding to IFNγ and IL-6 and the resulting inhibition of their activity were studied by means of extensive molecular-dynamics simulations. The effect of LMWH on IFNγ signalling inside stimulated WISH cells was investigated by measuring its antiproliferative activity and the translocation of phosphorylated STAT1 in the nucleus. We found that LMWH binds with high affinity to IFNγ and is able to fully inhibit the interaction with its cellular receptor. It also influences the biological activity of IL-6 by binding to either IL-6 or IL-6/IL-6Rα, thus preventing the formation of the IL-6/IL-6Rα/gp130 signalling complex. These findings shed light on the molecular mechanism of the anti-inflammatory action of LMWH and underpin its ability to influence favourably conditions characterised by overexpression of these two cytokines. Such conditions are not only associated with autoimmune diseases, but also with inflammatory processes, in particular with COVID-19. Our results put forward heparin as a promising means for the prevention and suppression of severe CRS and encourage further investigations on its applicability as an anti-inflammatory agent.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Interleukin-6
/
Interferon-gamma
/
Heparin, Low-Molecular-Weight
/
Anti-Inflammatory Agents
/
Anticoagulants
Limits:
Humans
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
Ijms221910730
Similar
MEDLINE
...
LILACS
LIS