Propolis from southeastern Brazil produced by Apis mellifera affects innate immunity by modulating cell marker expression, cytokine production and intracellular pathways in human monocytes

Abstract

Objectives Propolis is a bee-made product used for centuries due to its diverse biological properties, including its immunomodulatory action. This work aimed at investigating whether propolis may affect monocyte functions challenged with retinoic acid (RA), B subunit of Escherichia coli heat-labile enterotoxin (EtxB), human melanoma-associated antigen-1 (MAGE-1) and lipopolysaccharide (LPS). Methods Monocytes from healthy donors were treated with the stimuli separately or in the presence of propolis. Cell viability was evaluated by MTT assay, cell marker expression was assessed by flow cytometry, cytokine production by ELISA, gene expression by RT-qPCR. Key findings Propolis alone maintained TLR-2, TLR-4, HLA-DR, CD40 and CD80 expression in the monocytes; however, its combination with either MAGE-1 or LPS decreased CD40 expression triggered by the stimuli. Propolis maintained RA action on cell marker expression. Propolis inhibited TNF-α (with either EtxB or MAGE-1) and IL-6 (with either RA or MAGE-1), and increased IL-10 (with MAGE-1) production. Propolis downmodulated LC3 expression induced by LPS. It also induced a lower NF-kB expression than control cells and its combination with RA induced a higher expression than the stimulus alone. Conclusions Propolis potentially affected innate immunity by downmodulating the monocytes pro-inflammatory activity.

Brazilian green propolis: A novel tool to improve the cytotoxic and immunomodulatory action of docetaxel on MCF‐7 breast cancer cells and on women monocyte

“…The impaired interaction between CD80 and CD28 may lead lymphocytes to anergy or death, while the proper binding supports the activation of the Th1 profile, contributing to the antitumor immune response (Lahat et al, 2003;Mattern, Flad, Brade, Rietschel, & Ulmer, 1998;Wolk, Döcke, von Baehr, Volk, & Sabat, 2000). EEP enhanced CD80 expression induced by Escherichia coli enterotoxin B in human monocytes (Conte et al, 2021), what suggested that the effects of EEP + DTX on CD80 expression was due to DTX. In addition, this effect may also be due to the chemical composition of propolis, since another Brazilian sample-the red propolis-had an opposite effect on murine macrophages, inducing CD80 gene expression (Bueno-Silva et al, 2015).…”

The antiviral and immunomodulatory activities of propolis: An update and future perspectives for respiratory diseases

“…The immunomodulatory activity of propolis was shown to be independent from autophagy, since LC3 expression was not induced. In addition, propolis inhibited NF‐κB expression, downregulating monocyte inflammatory activity 123 . Even though the signaling pathways modulated in differentially polarized monocytes were not fully elucidated, propolis exerted an immunomodulatory activity oriented toward an anti‐inflammatory profile.…”

“…Additionally, the authors demonstrated that cytokine production was dependent on TLR-4 and could be abolished by blocking TLR-4. 122 Conte et al, 123 demonstrating once again that it may favor an anti-inflammatory milieu. In LPS-treated T h 17 polarized cells, propolis decreased CD40 expression and sustained LPS-induced IL-6 production.…”

“…Additionally, the authors demonstrated that cytokine production was dependent on TLR‐4 and could be abolished by blocking TLR‐4. 122 Conte et al, 123 after having identified Araucaria angustifolia (Bertol.) Kuntze, Baccharis dracunculifolia D.C., and Corymbia citriodora (Hook.)…”

“…In addition, propolis inhibited NF‐κB expression, downregulating monocyte inflammatory activity. 123 Even though the signaling pathways modulated in differentially polarized monocytes were not fully elucidated, propolis exerted an immunomodulatory activity oriented toward an anti‐inflammatory profile. These results, which appear sometimes inconsistent, show that the effects of propolis extract may be different, and even opposite, in relation to treatment concentrations and other less predictable experimental variables.…”