Immunomodulatory responses of peripheral blood mononuclear cells from multiple sclerosis patients upon in vitro incubation with the flavonoid luteolin: additive effects of IFN-β

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 MMP-9 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.

Identification of Small Molecule Activators of the Janus Kinase/Signal Transducer and Activator of Transcription Pathway Using a Cell-Based Screen

“…Luteolin has also been found to have an antiviral effect and shows a synergistic effect with IFN-β in modulating the immune responses of peripheral blood mononuclear cells isolated from multiple sclerosis patients, thus, it is proposed as a promising adjuvant for multiple sclerosis therapy. 21,22) Although its mechanism in these effects was still unknown, our finding that luteolin potently activated the JAK/ STAT pathway sheds new light on its preclinical study. Luteolin is found to be a protein kinase C (PKC) inhibitor, whereas PKCβ is found to negatively regulate IFN-induced JAK/STAT activation.…”

Mast cells and inflammation

“…We showed that luteolin can inhibit mast cell activation and mast cell-dependent superstimulation of activated T cells with or without stimulation by MBP [80]. Luteolin can also inhibit activation of peripheral lymphocytes from MS patients [311], and it was, therefore, proposed as adjuvant therapy for MS [312]. …”

Targeting IL-33 in Autoimmunity and Inflammation

“…Luteolin has synergistic effect with IFN-b in inhibiting activation of peripheral blood mononuclear cells from MS patients (Sternberg et al, 2008(Sternberg et al, , 2009. A novel luteolin analog, tetramethoxyluteolin, is more potent that luteolin (Weng et al, 2014b), making it an attractive molecule for drug development especially since it is also less metabolized (Walle, 2007).…”