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Synergistic effect of Avemar on proinflammatory cytokine production and Ras-mediated cell activation
András Telekes1, Endre Kiss-Tóth, Tünde Nagy
1Chemotherapy Day-Ward Unit, National Institute of Oncology, Ráth György u. 7-9, 1122 Budapest, Hungary. telekes@oncol.hu
Abstract:
Macrophages activated by lipopolysaccharide and/or phorbol esters exhibited high sensitivity to Avemar, a fermented wheat germ extract. Avemar synergized with lipopolysaccharide and PMA in the induction of the transcription of cytokine genes and release of inflammatory cytokines. At higher concentrations the preparation had a significant negative effect on the proliferation and survival of activated myeloid cell types. Avemar treatment induced the synthesis of ICAM-1 and synergized with the ICAM-inducing effect of TNF, but had no effect on VCAM-1 expression on microvascular endothelial cells. The effect of Avemar on signaling pathways, which are involved in cell activation was studied on HeLa cells as a model system. Avemar treatment increased the activity of stress kinases in a concentration-dependent way, resulting in the activation of AP-1 transcription factor. NF-kappa B-sensitive reporters were also activated by Avemar; in contrast, no effect of the preparation was observed on PKA-sensitive signaling pathways.
Insights
Avemar, a fermented wheat germ extract, modulates immune cell responses. It enhances cytokine production and immune cell activation, but inhibits proliferation at higher doses.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Macrophages are key immune cells involved in inflammatory responses.
- Lipopolysaccharide (LPS) and phorbol esters (PMA) are common activators of macrophages.
- Fermented wheat germ extract (Avemar) is explored for its biological effects.
Purpose of the Study:
- To investigate the effects of Avemar on activated immune cells and cellular signaling pathways.
- To determine Avemar's impact on cytokine gene expression and inflammatory cytokine release.
- To analyze Avemar's influence on cell proliferation, survival, and specific signaling pathways.
Main Methods:
- Macrophages were activated with LPS and/or PMA.
- Cytokine gene transcription and protein release were measured.
- Cell proliferation and survival assays were performed.
- Expression of ICAM-1 and VCAM-1 was assessed.
- HeLa cells were used to study signaling pathways (stress kinases, AP-1, NF-kappa B, PKA).
Main Results:
- Avemar sensitized activated macrophages, synergizing with LPS and PMA to induce cytokine gene transcription and release.
- Higher Avemar concentrations inhibited proliferation and survival of activated myeloid cells.
- Avemar induced ICAM-1 synthesis and synergized with TNF, but did not affect VCAM-1.
- Avemar activated stress kinases, AP-1, and NF-kappa B signaling pathways in a concentration-dependent manner.
- No effect of Avemar was observed on PKA-sensitive signaling pathways.
Conclusions:
- Avemar exhibits complex immunomodulatory effects, enhancing inflammatory responses while potentially inhibiting cell proliferation at higher concentrations.
- Avemar influences key signaling pathways involved in cell activation, including stress kinases, AP-1, and NF-kappa B.
- The findings suggest Avemar's potential as a modulator of immune cell function and inflammatory processes.
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