Immunomodulatory responses of peripheral blood mononuclear cells from multiple sclerosis patients upon in vitro incubati
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BioMed Central
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Immunomodulatory responses of peripheral blood mononuclear cells from multiple sclerosis patients upon in vitro incubation with the flavonoid luteolin: additive effects of IFN-β Zohara Sternberg*1, Kailash Chadha2, Alicia Lieberman2, Allison Drake1, David Hojnacki1, Bianca Weinstock-Guttman1 and Frederick Munschauer1 Address: 1Department of Neurology, Baird MS Center, Jacobs Neurological Institute, Buffalo, NY, USA and 2Department of Molecular & Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY, USA Email: Zohara Sternberg* - [email protected]; Kailash Chadha - [email protected]; Alicia Lieberman - [email protected]; Allison Drake - [email protected]; David Hojnacki - [email protected]; Bianca WeinstockGuttman - [email protected]; Frederick Munschauer - [email protected] * Corresponding author
Published: 13 October 2009 Journal of Neuroinflammation 2009, 6:28
doi:10.1186/1742-2094-6-28
Received: 21 July 2009 Accepted: 13 October 2009
This article is available from: http://www.jneuroinflammation.com/content/6/1/28 © 2009 Sternberg et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract The study is aimed to determine the role of luteolin (3',4',5,7-tetrahydroxyflavone), alone and in combination with human interferon-beta (IFN-β), 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 proinflammatory cytokines (IL-1β, TNF-α), 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-1β and TNF-α released by PBMCs in the culture supernatants. Luteolin reduced the MMP-9/TIMP-1 ratio via lowering MMP9 production. In the majority of cases, luteolin, when combined with IFN-β, had additive effects in modulating cell proliferation, IL-1β, TNF-α, MMP-9 and TIMP-1.
Background Flavonoids, are group of polyphenolic compounds, known to have significant anti-tumor, antioxidant and anti-inflammatory activities [1]. Epidemiological studies have shown that high intake of fruit and vegetables, rich in flavonoids, is protective against various forms of cancer [2], cardiovascular diseases [3] and neurodegenerative diseases [4]. Luteolin, 3',4',5,7-tetrahydroxyflavone, an important member of the flavonoid family has shown to exert immunomodulatory effects that may be beneficial in the treatment of neurodegenerative diseases such as multiple sclerosis (MS), which has an underlying T-cell mediated autoimmune pathology [5].
In vitro studies show that luteolin inhibits
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