Open Access

Preliminary results and a theoretical perspective of co‑treatment using a miR‑93‑5p mimic and aged garlic extract to inhibit the expression of the pro‑inflammatory interleukin‑8 gene

  • Authors:
    • Roberto Gambari
    • Chiara Papi
    • Jessica Gasparello
    • Enzo Agostinelli
    • Alessia Finotti
  • View Affiliations

  • Published online on: February 25, 2025     https://doi.org/10.3892/etm.2025.12835
  • Article Number: 85
  • Copyright: © Gambari et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The coronavirus disease‑19 (COVID‑19) pandemic has been a very significant health issue in the period between 2020 and 2023, forcing research to characterize severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) sequences and to develop novel therapeutic approaches. Interleukin‑6 (IL‑6) and IL‑8 are considered significant therapeutic targets for COVID‑19 and emerging evidence has suggested that microRNAs (miRNAs/miRs) serve a key role in regulating these genes. MiRNAs are short, 19‑25 nucleotides in length, non‑coding RNAs that regulate gene expression at the post‑transcriptional level through the sequence‑selective recognition of the 3'‑untranslated region (3'‑UTR) of the regulated mRNAs, eventually repressing translation, commonly, via mRNA degradation. For example, among several miRNAs involved in the regulation of the COVID‑19 ‘cytokine storm’, miR‑93‑5p can inhibit IL‑8 gene expression by directly targeting the 3'‑UTR of IL‑8 mRNA. In addition, miR‑93‑5p can regulate Toll‑like receptor‑4 (TLR4) and interleukin‑1 receptor‑associated kinase 4 (IRAK4) expression, thus affecting the nuclear factor‑κB (NF‑κB) pathway and the expression of NF‑κB‑regulated genes, such as IL‑6, IL‑1β and other hyper‑expressed genes during the COVID‑19 ‘cytokine storm’. In the present study, the results provided preliminary evidence suggesting that the miR‑93‑5p‑based miRNA therapeutics could be combined with the anti‑inflammatory aged garlic extract (AGE) to more effectively inhibit IL‑8 gene expression. The human bronchial epithelial IB3‑1 cell line was employed as experimental model system. IB3‑1 cells were stimulated with the BNT162b2 COVID‑19 vaccine and transfected with pre‑miR‑93‑5p in the absence or in the presence of AGE, to verify the inhibitory effects on the BNT162b2‑induced expression of the IL‑8 gene. The accumulation of IL‑8 mRNA was assessed by RT‑qPCR; the release of IL‑8 protein was determined by Bio‑Plex assay. In addition, the possible applications of TLR4/NF‑κB inhibitory agents (such as miR‑93‑5p and AGE) for treating human pathologies at a hyperinflammatory state, such as COVID‑19, cystic fibrosis and other respiratory diseases, were summarized.
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April-2025
Volume 29 Issue 4

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Spandidos Publications style
Gambari R, Papi C, Gasparello J, Agostinelli E and Finotti A: Preliminary results and a theoretical perspective of co‑treatment using a miR‑93‑5p mimic and aged garlic extract to inhibit the expression of the pro‑inflammatory interleukin‑8 gene. Exp Ther Med 29: 85, 2025.
APA
Gambari, R., Papi, C., Gasparello, J., Agostinelli, E., & Finotti, A. (2025). Preliminary results and a theoretical perspective of co‑treatment using a miR‑93‑5p mimic and aged garlic extract to inhibit the expression of the pro‑inflammatory interleukin‑8 gene. Experimental and Therapeutic Medicine, 29, 85. https://doi.org/10.3892/etm.2025.12835
MLA
Gambari, R., Papi, C., Gasparello, J., Agostinelli, E., Finotti, A."Preliminary results and a theoretical perspective of co‑treatment using a miR‑93‑5p mimic and aged garlic extract to inhibit the expression of the pro‑inflammatory interleukin‑8 gene". Experimental and Therapeutic Medicine 29.4 (2025): 85.
Chicago
Gambari, R., Papi, C., Gasparello, J., Agostinelli, E., Finotti, A."Preliminary results and a theoretical perspective of co‑treatment using a miR‑93‑5p mimic and aged garlic extract to inhibit the expression of the pro‑inflammatory interleukin‑8 gene". Experimental and Therapeutic Medicine 29, no. 4 (2025): 85. https://doi.org/10.3892/etm.2025.12835