Complexes of Oligoribonucleotides with D-Mannitol Modulate the Innate Immune Response to Influenza A Virus H1N1 (A/FM/1/47) In Vivo

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2018 Jul 25

PMID 30037133

Citations 3

Authors

Nataliia Melnichuk

Vladimir Kashuba

Svitlana Rybalko

Zenoviy Tkachuk

Affiliations

Soon will be listed here.

Abstract

Rapid replication of the influenza A virus and lung tissue damage caused by exaggerated pro-inflammatory host immune responses lead to numerous deaths. Therefore, novel therapeutic agents that have anti-influenza activities and attenuate excessive pro-inflammatory responses that are induced by an influenza virus infection are needed. Oligoribonucleotides-d-mannitol (ORNs-d-M) complexes possess both antiviral and anti-inflammatory activities. The current research was aimed at studying the ORNs-d-M effects on expression of innate immune genes in mice lungs during an influenza virus infection. Expression of genes was determined by RT-qPCR and Western blot assays. In the present studies, we found that the ORNs-d-M reduced the influenza-induced up-expression of Toll-like receptors (TLRs) (, , ), nuclear factor NF-kB (, ), cytokines (, , , , , , , , ), chemokines (, , , , , ), interferon-stimulated genes (ISGs) (, , , ), and pro-oxidation (, ) genes. The ORNs-d-M inhibited the mRNA overexpression of , , and induced by the influenza virus, which suggests that they impair the upregulation of NF-kB, cytokines, chemokines, ISGs, and pro-oxidation genes induced by the influenza virus by inhibiting activation of the TLR-3, TLR-7, and TLR-8 signaling pathways. By impairing activation of the TLR-3, TLR-7, and TLR-8 signaling pathways, the ORNs-d-M can modulate the innate immune response to an influenza virus infection.

Citing Articles

The Natural Oligoribonucleotides Functionalized by D-Mannitol Affected Interactions of Hemagglutinin with Glycan Receptor Indicating Anti-Influenza Activity.

Tkachuk Z, Melnichuk N, Nikolaiev R, Szutkowski K, Zhukov I Membranes (Basel). 2021; 11(10).

PMID: 34677523 PMC: 8538433. DOI: 10.3390/membranes11100757.

Transcriptome Analysis Reveals Possible Immunomodulatory Activity Mechanism of sp. Exopolysaccharides on RAW264.7 Macrophages.

Wu S, Liu H, Li S, Sun H, He X, Huang Y Mar Drugs. 2021; 19(4).

PMID: 33919822 PMC: 8070752. DOI: 10.3390/md19040217.

The Potential Protective Effect of Oligoribonucleotides-d-Mannitol Complexes against Thioacetamide-Induced Hepatotoxicity in Mice.

Marchyshak T, Yakovenko T, Shmarakov I, Tkachuk Z Pharmaceuticals (Basel). 2018; 11(3).

PMID: 30082619 PMC: 6161262. DOI: 10.3390/ph11030077.

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