title: C3 binding glycoprotein from Cuscuta europea induced different cytokine profiles from human PBMC compared to other plant and bacterial immunomodulators.
abstract: The immunomodulatory properties of bioactive agents include the ability to induce cytokine production by the activated target cell. The effect of immunomodulatory C3 binding glycoprotein isolated from Cuscuta europea on the induction of human PBMC cytokine synthesis and the cell viability was investigated. Isolated PBMC from healthy donors were cultured for 24 h with C3bgp. We also studied the influence of C3bgp on the cytokine production in LPS, PHA, PWM and Dex treated PBMC. The quantitative determination of TNF-alpha, IL-12, IL-6 and IL-10 was performed in culture supernatant by ELISA. Results obtained demonstrated that C3bgp induced proinflammatory and immunoregulatory cytokine production, in the highest degree IL-12, followed by IL-6 and in lower degree TNF-alpha. IL-12 quantity was significantly increased in C3bgp stimulated cultures in comparison with LPS, PHA and PWM stimulated PBMC. C3bgp also increased IL-12 in PHA or PWM stimulated cultures, but not in LPS stimulated culture. C3bgp significantly increased IL-6 production compared to the PHA and PWM but not to LPS stimulation. On the other side, C3bgp inhibited IL-10 production after LPS, PHA and PWM stimulation. Cell viability in C3bgp stimulated cultures retained on the same level from 72 to 120 h of culturing, in contrast to LPS and PHA stimulated cultures. Based on the results presented, we conclude that the C3bgp exhibited immunomodulatory properties on the human PBMC. The ability of PDTC and Dex to down-regulate the effect of C3bgp on the proinflammatory cytokine production suggests that a part of the mechanism of action of C3bgp is mediated through NF-kB signal transduction pathway.
authors.affiliation: Department of Molecular Biology, Immunology and Genetics, Faculty of Medicine, Trakia University, Armeiska 11 St., 6000 Stara Zagora, Bulgaria. stanilova@mf.uni-sz.bg
authors.forename: Spaska A
authors.initials: SA
authors.lastname: Stanilova
authors.forename: Zlatka G
authors.initials: ZG
authors.lastname: Dobreva
authors.forename: Emil S
authors.initials: ES
authors.lastname: Slavov
authors.forename: Lyuba D
authors.initials: LD
authors.lastname: Miteva
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D002478:Cells, Cultured; D003176:Complement C3 / Q000737:chemistry; D034182:Cuscuta / Q000737:chemistry*; D016207:Cytokines / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006023:Glycoproteins / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010940:Plant Proteins / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D000276:Adjuvants, Immunologic; D003176:Complement C3; D016207:Cytokines; D006023:Glycoproteins; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D010940:Plant Proteins; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D003907:Dexamethasone