Ghoneum, PhD, a and A. Jewett, PhD
Department of Otolaryngology, Charles R. Drew University of Medicine and Science, Departments of Neurobiology and Microbiology and Immunology, University of California at Los Angeles Schools of Medicine and Dentistry, Los Angeles, CA
Address all correspondence and reprint requests to: Mamdooh Ghoneum, PhD, Drew University of Medicine and Science, Department of Otolaryngology, J 621 East !20th Street, Los Angeles, CA 90059.
Recently, we presented evidence for the role of MGN-3, an enzymatically modified arabinoxylan extracted from rice bran, in potent activation of human natural killer (NK) cell function in vivo and in vitro. In the current study, we examined the mechanism by which MGN-3 elevated NK cytotoxic activity. We did this by testing the action of MGN-3 on the levels of both tumor necrosis factor- α (TNF- α) and interferon-γ (IFN-γ) secretions and MGN-3 function on the expression of key cell surface receptors. Peripheral blood lymphocytes were treated with MGN-3 at concentrations of 0.1 mg/ml ai1d 1 mg/ml, and supernatants were subjected to enzyme linked immnunosorbent assay. Results showed that MGN-3 is a potent TNF-α inducer. The effect was dose-dependent. MGN-3 concentration at 0.1 and 1 mg/ml increased TNF-α production by 22.8- and 47.1-fold, respectively. MGN-3 also increased production of IFN-γ but at lower levels as compared to TNF-a. With respect to key cell surface receptors, MGN-3 increases the expression of CD69, an early activation antigen at I 6 hours after treatment. Furthermore, the interleukin-2 receptor CD25 and the adhesion molecule ICAM-1 (CD54) were upregulated after treatment with MGN-3. Treating highly purified NK cells with MGN-3 also resulted in increased levels of TNF-α and IFN-γ secretion in conjunction with augmentation of NK cell cytotoxic function. Furthermore, addition of MGN-3 to interleukin-2-activated NK cells resulted in a synergistic induction of TNF-α and IFN-γ secretion. Overall, our data suggest that MGN-3, a novel biological response modifier, can be used as a safe alternative or as an adjuvant to the existing immunotherapeutic modalities.
KEY WORDS: Arabinoxylan, interleukin-2, MGN-3, Biobran, natural killer cell, synergy, TNF-α