Sulforaphane Inhibits the Expression of Interleukin-6 and Interleukin-8 Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein

Overview

Journal Phytomedicine

Specialty Rehabilitation Medicine

Date 2021 May 25

PMID 34033999

Citations 19

Authors

Jessica Gasparello

Elisabetta DAversa

Chiara Papi

Laura Gambari

Brunella Grigolo

Monica Borgatti

Alessia Finotti

Roberto Gambari

Affiliations

Soon will be listed here.

Abstract

Background: A key clinical feature of COVID-19 is a deep inflammatory state known as "cytokine storm" and characterized by high expression of several cytokines, chemokines and growth factors, including IL-6 and IL-8. A direct consequence of this inflammatory state in the lungs is the Acute Respiratory Distress Syndrome (ARDS), frequently observed in severe COVID-19 patients. The "cytokine storm" is associated with severe forms of COVID-19 and poor prognosis for COVID-19 patients. Sulforaphane (SFN), one of the main components of Brassica oleraceae L. (Brassicaceae or Cruciferae), is known to possess anti-inflammatory effects in tissues from several organs, among which joints, kidneys and lungs.

Purpose: The objective of the present study was to determine whether SFN is able to inhibit IL-6 and IL-8, two key molecules involved in the COVID-19 "cytokine storm".

Methods: The effects of SFN were studied in vitro on bronchial epithelial IB3-1 cells exposed to the SARS-CoV-2 Spike protein (S-protein). The anti-inflammatory activity of SFN on IL-6 and IL-8 expression has been evaluated by RT-qPCR and Bio-Plex analysis.

Results: In our study SFN inhibits, in cultured IB3-1 bronchial cells, the gene expression of IL-6 and IL-8 induced by the S-protein of SARS-CoV-2. This represents the proof-of-principle that SFN may modulate the release of some key proteins of the COVID-19 "cytokine storm".

Conclusion: The control of the cytokine storm is one of the major issues in the management of COVID-19 patients. Our study suggests that SFN can be employed in protocols useful to control hyperinflammatory state associated with SARS-CoV-2 infection.

Citing Articles

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Gasparello J, Papi C, Marzaro G, Macone A, Zurlo M, Finotti A Molecules. 2025; 29(24.

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Anti-Inflammatory Therapeutic Mechanisms of Isothiocyanates: Insights from Sulforaphane.

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References

Andreakos E, Papadaki M, Serhan C . Dexamethasone, pro-resolving lipid mediators and resolution of inflammation in COVID-19. Allergy. 2020; 76(3):626-628. PMC: 7537007. DOI: 10.1111/all.14595. View

Gao S, Zhang L . ACE2 partially dictates the host range and tropism of SARS-CoV-2. Comput Struct Biotechnol J. 2020; 18:4040-4047. PMC: 7700767. DOI: 10.1016/j.csbj.2020.11.032. View

Wang Z, Wang Y, Vilekar P, Yang S, Gupta M, Oh M . Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide. PeerJ. 2020; 8:e9533. PMC: 7350920. DOI: 10.7717/peerj.9533. View

Gasparello J, Gambari L, Papi C, Rozzi A, Manicardi A, Corradini R . High Levels of Apoptosis Are Induced in the Human Colon Cancer HT-29 Cell Line by Co-Administration of Sulforaphane and a Peptide Nucleic Acid Targeting miR-15b-5p. Nucleic Acid Ther. 2020; 30(3):164-174. DOI: 10.1089/nat.2019.0825. View

Grasselli G, Tonetti T, Protti A, Langer T, Girardis M, Bellani G . Pathophysiology of COVID-19-associated acute respiratory distress syndrome: a multicentre prospective observational study. Lancet Respir Med. 2020; 8(12):1201-1208. PMC: 7834127. DOI: 10.1016/S2213-2600(20)30370-2. View

Zeitlin P, Lu L, Rhim J, Cutting G, Stetten G, Kieffer K . A cystic fibrosis bronchial epithelial cell line: immortalization by adeno-12-SV40 infection. Am J Respir Cell Mol Biol. 1991; 4(4):313-9. DOI: 10.1165/ajrcmb/4.4.313. View

Matveeva T, Khafizova G, Sokornova S . In Search of Herbal Anti-SARS-Cov2 Compounds. Front Plant Sci. 2020; 11:589998. PMC: 7701093. DOI: 10.3389/fpls.2020.589998. View

Burke H, Freeman A, Cellura D, Stuart B, Brendish N, Poole S . Inflammatory phenotyping predicts clinical outcome in COVID-19. Respir Res. 2020; 21(1):245. PMC: 7506817. DOI: 10.1186/s12931-020-01511-z. View

Soumagne T, Winiszewski H, Besch G, Mahr N, Senot T, Costa P . Pulmonary embolism among critically ill patients with ARDS due to COVID-19. Respir Med Res. 2020; 78:100789. PMC: 7494436. DOI: 10.1016/j.resmer.2020.100789. View

10.

Wang W, Ye L, Ye L, Li B, Gao B, Zeng Y . Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway. Virus Res. 2007; 128(1-2):1-8. PMC: 7114322. DOI: 10.1016/j.virusres.2007.02.007. View

11.

de Simone G, Mancusi C . Finding the right time for anti-inflammatory therapy in COVID-19. Int J Infect Dis. 2020; 101:247-248. PMC: 7528747. DOI: 10.1016/j.ijid.2020.09.1454. View

12.

Del Valle D, Kim-Schulze S, Huang H, Beckmann N, Nirenberg S, Wang B . An inflammatory cytokine signature predicts COVID-19 severity and survival. Nat Med. 2020; 26(10):1636-1643. PMC: 7869028. DOI: 10.1038/s41591-020-1051-9. View

13.

Pelaia C, Tinello C, Vatrella A, De Sarro G, Pelaia G . Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications. Ther Adv Respir Dis. 2020; 14:1753466620933508. PMC: 7298425. DOI: 10.1177/1753466620933508. View

14.

Subedi L, Lee J, Yumnam S, Ji E, Kim S . Anti-Inflammatory Effect of Sulforaphane on LPS-Activated Microglia Potentially through JNK/AP-1/NF-κB Inhibition and Nrf2/HO-1 Activation. Cells. 2019; 8(2). PMC: 6406309. DOI: 10.3390/cells8020194. View

15.

Qi T, Xu F, Yan X, Li S, Li H . Sulforaphane exerts anti-inflammatory effects against lipopolysaccharide-induced acute lung injury in mice through the Nrf2/ARE pathway. Int J Mol Med. 2015; 37(1):182-8. DOI: 10.3892/ijmm.2015.2396. View

16.

Latte K, Appel K, Lampen A . Health benefits and possible risks of broccoli - an overview. Food Chem Toxicol. 2011; 49(12):3287-309. DOI: 10.1016/j.fct.2011.08.019. View

17.

Dzobo K, Chiririwa H, Dandara C, Dzobo W . Coronavirus Disease-2019 Treatment Strategies Targeting Interleukin-6 Signaling and Herbal Medicine. OMICS. 2020; 25(1):13-22. DOI: 10.1089/omi.2020.0122. View

18.

Gasparello J, Lomazzi M, Papi C, DAversa E, Sansone F, Casnati A . Efficient Delivery of MicroRNA and AntimiRNA Molecules Using an Argininocalix[4]arene Macrocycle. Mol Ther Nucleic Acids. 2019; 18:748-763. PMC: 6859282. DOI: 10.1016/j.omtn.2019.09.029. View

19.

Zeng Z, Yu H, Chen H, Qi W, Chen L, Chen G . Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China. Crit Care. 2020; 24(1):525. PMC: 7450961. DOI: 10.1186/s13054-020-03255-0. View

20.

Pei Y, Wu B, Cao Q, Wu L, Yang G . Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells. Toxicol Appl Pharmacol. 2011; 257(3):420-8. DOI: 10.1016/j.taap.2011.09.026. View