title: Production of tumor necrosis factor-alpha and interferon-gamma from human peripheral blood lymphocytes by MGN-3, a modified arabinoxylan from rice bran, and its synergy with interleukin-2 in vitro.
abstract: 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-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) 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 and 1 mg/ml, and supernatants were subjected to enzyme-linked immunosorbent assay. Results showed that MGN-3 is a potent TNF-alpha inducer. The effect was dose-dependent. MGN-3 concentration at 0.1 and 1 mg/ml increased TNF-alpha production by 22.8- and 47. 1-fold, respectively. MGN-3 also increased production of IFN-gamma but at lower levels as compared to TNF-alpha With respect to key cell surface receptors, MGN-3 increases the expression of CD69, an early activation antigen at 16 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-alpha and IFN-gamma 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-alpha and IFN-gamma 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.
authors.affiliation: Department of Otolaryngology, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ghoneum
authors.forename: A
authors.initials: A
authors.lastname: Jewett
mesh_terms: D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000378:metabolism; D037181:Lectins, C-Type; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011336:Probability; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013194:Staining and Labeling; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation; D014990:Xylans / Q000494:pharmacology*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007155:Immunologic Factors; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D007376:Interleukin-2; D037181:Lectins, C-Type; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D014990:Xylans; D000099192:CD69 Antigens; C419427:polysaccharide MGN3; C085118:arabinoxylan