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Title

Interferon-β induces hepatocyte growth factor in monocytes of multiple sclerosis patients
Authors
Molnarfi, Nicolas
Benkhoucha, Mahdia
Bjarnadottir, Kristbjorg
Juillard Mochon, Catherine
Lalive d'Epinay, Patrice
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 Adult — Blotting, Western — Enzyme-Linked Immunosorbent Assay — Female — Flow Cytometry — Gene Expression Regulation/drug effects — Hepatocyte Growth Factor/biosynthesis — Humans — Interferon-beta/pharmacology/therapeutic use — Leukocytes, Mononuclear/metabolism — Male — Middle Aged — Multiple Sclerosis/drug therapy/metabolism — Proto-Oncogene Proteins c-met/metabolism — Reverse Transcriptase Polymerase Chain Reaction — Switzerland
Identifiers
PMID: 23166786
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Article (Published version) (660 Kb) - public document Free access
Structures
Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques
Research group Scléroses en plaques, neuroimmunologie, encéphalite autoimmune expérimentale (843)
Citation
(ISO format) 		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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