P38 mitogen-activated protein kinase inhibition enhances invitro erythropoiesis of Fanconi anemia, complementation group A-deficient bonemarrow cells

Johanna Svahn, Tiziana Lanza, Keaney Rathbun, Grover Bagby, Silvia Ravera, Fabio Corsolini, Angela Pistorio, Daniela Longoni, Piero Farruggia, Carlo Dufour, Enrico Cappelli

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Bone marrow failure in Fanconi anemia (FA) has been linked in part to overproduction of inflammatory cytokines, to which FA stem and progenitor cells are hypersensitive. In cell lines and murine models p38 mitogen-activated protein kinase (MAPK)-dependent tumor necrosis factor α (TNF-α) overexpression can be induced by the Toll-like receptors (TLRs) 4 and 7/8 ligands Lipopolysaccharide (LPS) and R848. Exvivo exposure of FA stem cells to TNF-α suppresses their replication and selects preleukemic clones. Here we show that inhibition of p38 MAPK also reduces TLR4 and 7/8-mediated TNF-α production in primary human FA complementation group A (FANCA)-deficient monocytes from nine patients and demonstrate that, while p38 MAPK inhibition also enhances clonal growth of FANCA-deficient erythroid progenitors, the effect was mediated indirectly by the influence of the inhibitor on auxiliary cells, not erythroid colony-forming units themselves. Taken together, these results support the view that inhibition of the p38 MAPK pathway in monocytes may improve hematopoiesis in FANCA patients.

    Original languageEnglish (US)
    Pages (from-to)295-299
    Number of pages5
    JournalExperimental Hematology
    Volume43
    Issue number4
    DOIs
    StatePublished - Apr 1 2015

    Fingerprint

    Fanconi Anemia
    Erythropoiesis
    p38 Mitogen-Activated Protein Kinases
    Stem Cells
    Monocytes
    resiquimod
    Toll-Like Receptor 7
    Erythroid Precursor Cells
    Toll-Like Receptor 4
    Hematopoiesis
    Lipopolysaccharides
    Clone Cells
    Tumor Necrosis Factor-alpha
    Bone Marrow
    Cytokines
    Ligands
    Cell Line
    Growth

    ASJC Scopus subject areas

    • Cancer Research
    • Cell Biology
    • Genetics
    • Molecular Biology
    • Hematology
    • Medicine(all)

    Cite this

    P38 mitogen-activated protein kinase inhibition enhances invitro erythropoiesis of Fanconi anemia, complementation group A-deficient bonemarrow cells. / Svahn, Johanna; Lanza, Tiziana; Rathbun, Keaney; Bagby, Grover; Ravera, Silvia; Corsolini, Fabio; Pistorio, Angela; Longoni, Daniela; Farruggia, Piero; Dufour, Carlo; Cappelli, Enrico.

    In: Experimental Hematology, Vol. 43, No. 4, 01.04.2015, p. 295-299.

    Research output: Contribution to journalArticle

    Svahn, J, Lanza, T, Rathbun, K, Bagby, G, Ravera, S, Corsolini, F, Pistorio, A, Longoni, D, Farruggia, P, Dufour, C & Cappelli, E 2015, 'P38 mitogen-activated protein kinase inhibition enhances invitro erythropoiesis of Fanconi anemia, complementation group A-deficient bonemarrow cells', Experimental Hematology, vol. 43, no. 4, pp. 295-299. https://doi.org/10.1016/j.exphem.2014.11.010
    Svahn, Johanna ; Lanza, Tiziana ; Rathbun, Keaney ; Bagby, Grover ; Ravera, Silvia ; Corsolini, Fabio ; Pistorio, Angela ; Longoni, Daniela ; Farruggia, Piero ; Dufour, Carlo ; Cappelli, Enrico. / P38 mitogen-activated protein kinase inhibition enhances invitro erythropoiesis of Fanconi anemia, complementation group A-deficient bonemarrow cells. In: Experimental Hematology. 2015 ; Vol. 43, No. 4. pp. 295-299.
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