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Interferon-β induces hepatocyte growth factor in monocytes of multiple sclerosis patients

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Published in PLOS ONE. 2012, vol. 7, no. 11, p. e49882
Abstract Interferon-β is a first-line therapy used to prevent relapses in relapsing-remitting multiple sclerosis. The clinical benefit of interferon-β in relapsing-remitting multiple sclerosis is attributed to its immunomodulatory effects on inflammatory mediators and T cell reactivity. Here, we evaluated the production of hepatocyte growth factor, a neuroprotective and neuroinflammation-suppressive mediator, by peripheral blood mononuclear cells collected from interferon-β--treated relapsing-remitting multiple sclerosis patients, relapsing remitting multiple sclerosis patients not treated with interferon-β, and healthy volunteers. Using intracellular flow cytometry analysis, increased production of hepatocyte growth factor was observed in circulating CD14(+) monocytes from patients undergoing long-term treatment with interferon-β versus untreated patients. Complementary in vitro studies confirmed that treatment with interferon-β induced rapid and transient transcription of the hepatocyte growth factor gene in CD14(+) monocytes and that intracellular and secreted monocytic hepatocyte growth factor protein levels were markedly stimulated by interferon-β treatment. Additional exploration revealed that "pro-inflammatory" (CD14(+)CD16(+)) monocytes produced similar levels of hepatocyte growth factor in response to interferon-β as "classical" (CD14(+)CD16(-)) monocytes, and that CD14(+) monocytes but not CD4(+) T cells express the hepatocyte growth factor receptor c-Met. Our findings suggest that interferon-β may mediate some of its therapeutic effects in relapsing-remitting multiple sclerosis through the induction of hepatocyte growth factor by blood monocytes by coupling immune regulation and neuroprotection.
Keywords AdultBlotting, WesternEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryGene Expression Regulation/drug effectsHepatocyte Growth Factor/biosynthesisHumansInterferon-beta/pharmacology/therapeutic useLeukocytes, Mononuclear/metabolismMaleMiddle AgedMultiple Sclerosis/drug therapy/metabolismProto-Oncogene Proteins c-met/metabolismReverse Transcriptase Polymerase Chain ReactionSwitzerland
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PMID: 23166786
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Article (Published version) (660 Kb) - public document Free access
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Research group Scléroses en plaques, neuroimmunologie, encéphalite autoimmune expérimentale (843)
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MOLNARFI, Nicolas et al. Interferon-β induces hepatocyte growth factor in monocytes of multiple sclerosis patients. In: PLOS ONE, 2012, vol. 7, n° 11, p. e49882. https://archive-ouverte.unige.ch/unige:32671

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Deposited on : 2013-12-23

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