Novel effect of methionine enkephalin against influenza A virus infection through inhibiting TLR7-MyD88-TRAF6-NF-κB p65 signaling pathway.

Abstract

The morbidity and mortality associated with influenza A virus infections, have stimulated the search for novel prophylactic and therapeutic drugs. The purpose of this study was to investigate the prophylactic and therapeutic effect of synthetic methionine enkephalin (MENK) on mice infected by A/PR/8/34 influenza virus (H1N1) in vivo. The results showed that MENK could exert both prophylactic and therapeutic influences on infected mice, significantly improve the survival rate, relieve acute lung injury and decrease cytokine (IFN-α, IFN-β, TNF-α, IL-6, and IL-1β) levels. MENK also inhibited virus replication on day 4 post infection (p.i.) through upregulating opioid receptors (MOR, DOR) and suppressing TLR7-MyD88-TRAF6-NF-κB p65 signaling pathways. These results suggest that MENK, given via intranasal administration, could provide a novel drug with a new mode of action as a nonspecific anti-influenza agent or vaccine adjuvant.

• Authors: Jing Tian, Xue Jiao, Xiaonan Wang, Jin Geng, Reizhe Wang, Ning Liu, Xinhua Gao, Noreen Griffin, Fengping Shan
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 55 Pg. 38-48 (Feb 2018) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 29220721 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antiviral Agents
• Cytokines
• Inflammation Mediators
• Membrane Glycoproteins
• Myeloid Differentiation Factor 88
• NF-kappa B
• Receptors, Opioid
• TNF Receptor-Associated Factor 6
• Tlr7 protein, mouse
• Toll-Like Receptor 7
• Enkephalin, Methionine

Topics

• Animals
• Antiviral Agents (therapeutic use)
• Cytokines (metabolism)
• Enkephalin, Methionine (therapeutic use)
• Female
• Humans
• Inflammation Mediators (metabolism)
• Influenza A Virus, H1N1 Subtype (physiology)
• Influenza, Human (drug therapy)
• Lung (metabolism, pathology)
• Membrane Glycoproteins (metabolism)
• Mice
• Mice, Inbred C57BL
• Myeloid Differentiation Factor 88 (metabolism)
• NF-kappa B (metabolism)
• Orthomyxoviridae Infections (drug therapy)
• Receptors, Opioid (metabolism)
• Signal Transduction
• TNF Receptor-Associated Factor 6 (metabolism)
• Toll-Like Receptor 7 (metabolism)
• Virus Replication