Synergistic Effect of Avemar on Proinflammatory Cytokine Production and Ras-Mediated Cell Activation


Address for correspondence: András Telekes, M.D., Ph.D., Head, Chemotherapy Day-Ward Unit, National Institute of Oncology, Ráth György u. 7-9, 1122 Budapest, Hungary. Voice: +36-1-224-8600; fax: +36-1-224-8620.


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.