Gene Expression Pattern of Peyer's Patch Lymphocytes Exposed to Kagocel Suggests Pattern-Recognition Receptors Mediate Its Action.
Peyer’s patch lymphocytes
cytokines
gene expression
kagocel
pattern recognition receptors
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
12
03
2021
accepted:
16
07
2021
entrez:
20
8
2021
pubmed:
21
8
2021
medline:
21
8
2021
Statut:
epublish
Résumé
Kagocel is a synthetic carboxymethylcellulose derivative copolymerized with gossypol. Clinical data evidence its safety and efficiency for the treatment of flu and other viral infections via enhancement of interferon production. The gut-associated lymphoid tissue seems a likely site of kagocel action. The study was aimed to investigate the molecular mechanisms of its action using murine Peyer's patches lymphocytes as a test system and the cytokines production and gene expression patterns as the primary outcomes. The Peyer's patches lymphocytes isolated from BALB/c mice were stimulated with concanavalin A, or, to mimic viral infection, with a combination of concanavalin A and TLR3 ligand poly I:C. After 24 h of stimulation the cells were treated with saline, 30, 100, or 300 μg/ml of kagocel, or, as positive controls, 300 μg/ml oats b-D-glucan or 300 μg/ml lentinan. After 24 and 72 h of incubation with these drugs cytokines production was analyzed with ELISA and gene expression pattern was investigated using nCounter Inflammation panel chips followed by bioinformatics analysis. Expression of genes involved in the inflammatory response, antiviral defense, lymphocytes survival and proliferation (C1qa, C2, C3, Ccl21a, Il11, Il1b, Il23a, Il5, Ltb4r2, Alox15, Pla2g4a, Ptger1, Mapkapk5, Hras, Ifna1, Tlr2, Mrc1, Mx2) was upregulated in kagocel-treated Peyer's patches lymphocytes. A list of plausible transcription factors (CEBPs, IRF, NFκB, RXR, Stat, Tead4, and ZSCAN) and master-regulators has been identified (cIAP, CIKS, dock9, MEKK1, FXR, IKK, IRAK, TRAF, dsRNA:TLR3:TRIF). The changes in gene expression pattern and the outcomes of bioinformatics analysis suggest that pattern recognition receptors, TLRs and dectin-1, are the key mediators of kagocel immunomodulatory action, with the possible involvement of interferon autocrine loop. The genes upregulated with kagocel include diverse components of the innate immune defense system.
Identifiants
pubmed: 34413772
doi: 10.3389/fphar.2021.679511
pii: 679511
pmc: PMC8369352
doi:
Types de publication
Journal Article
Langues
eng
Pagination
679511Informations de copyright
Copyright © 2021 Andreev-Andrievskiy, Zinovkin, Mashkin, Frolova, Kazaishvili, Scherbakova, Rudoy and Nesterenko.
Déclaration de conflit d'intérêts
The reviewer AZ declared a past co-authorship with one of the authors RZ to the handling editor. The study was performed by MSU Institute for mitoengineering by contract with Nearmedic, LLC. The funder, acting as a study sponsor, had approved the study design, but had no role in data collection, analysis and interpretation or the decision to publish.
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