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- Title
Complexes of Oligoribonucleotides with D-Mannitol Modulate the Innate Immune Response to Influenza A Virus H1N1 (A/FM/1/47) In Vivo.
- Authors
Melnichuk, Nataliia; Kashuba, Vladimir; Rybalko, Svitlana; Tkachuk, Zenoviy
- 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) (tlr3, tlr7, tlr8), nuclear factor NF-kB (nfkbia, nfnb1), cytokines (ifn#, ifnk, ifna2, ifnb1, ifng, il6, il1b, il12a, tnf), chemokines (ccl3, ccl4, ccl5, cxcl9, cxcl10, cxcl11), interferon-stimulated genes (ISGs) (oas1a, oas2, oas3, mx1), and pro-oxidation (nos2, xdh) genes. The ORNs-D-M inhibited the mRNA overexpression of tlr3, tlr7, and tlr8 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.
- Subjects
RIBONUCLEOTIDES; MANNITOL; NATURAL immunity; INFLUENZA A virus, H1N1 subtype; GENE expression; INTERFERONS; THERAPEUTICS
- Publication
Pharmaceuticals (14248247), 2018, Vol 11, Issue 3, p73
- ISSN
1424-8247
- Publication type
Article
- DOI
10.3390/ph11030073