Immunomodulatory responses of peripheral blood mononuclear cells from multiple sclerosis patients upon in vitro incubation with the flavonoid luteolin: additive effects of IFN-beta.
The study is aimed to determine the role of luteolin (3',4',5,7-tetrahydroxyflavone), alone and in combination with human interferon-beta (IFN-beta), in modulating the immune response(s) of peripheral blood mononuclear cells (PBMCs) isolated from multiple sclerosis (MS) patients. PBMC proliferation in the presence or absence of these drugs was determined and the production of pro-inflammatory cytokines (IL-1beta, TNF-alpha), and the ratio of cell migration mediator MMP-9, and its inhibitor, TIMP-1 was assessed in the culture supernatants. Luteolin reduced, in a dose-dependent manner, the proliferation of PBMCs, and modulated the levels of IL-1beta and TNF-alpha released by PBMCs in the culture supernatants. Luteolin reduced the MMP-9/TIMP-1 ratio via lowering MMP-9 production. In the majority of cases, luteolin, when combined with IFN-beta, had additive effects in modulating cell proliferation, IL-1beta, TNF-alpha, MMP-9 and TIMP-1.
Sternberg
Zohara
Z
Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, USA. zs2@buffalo.edu
Chadha
Kailash
K
Lieberman
Alicia
A
Drake
Allison
A
Hojnacki
David
D
Weinstock-Guttman
Bianca
B
Munschauer
Frederick
F
D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D016899:Interferon-beta / Q000276:immunology*; D053583:Interleukin-1beta / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D047311:Luteolin / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D015394:Molecular Structure; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007155:Immunologic Factors; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D020780:Matrix Metalloproteinase 9; D047311:Luteolin