title: Lyprinol inhibits LTB4 production by human monocytes.
abstract: The effect of Lyprinol was evaluated on LTB4-induced human monocytes (normal and allergic donors) activation. Peripheral blood normal monocyte-derived monocytes when stimulated by Interleukin-4 (IL-4) produced high amounts of leukotriene B4 (LTB4) through the activation of the 5-lipoxygenase pathway. Maximal effect was observed in the presence of 10 ng/ml IL-4, and maximal LTB4 production was reached 40 min after the onset of stimulation. When stimulated for 48 h with IL-4, resting human monocytes expressed and released the low affinity receptor for IgE (CD23), and were inhibited in the presence of Lyprinol, or of the non redox 5-lipoxygenase inhibitor (BW B70C), suggesting that the production of LTB4 partially contributed to the IL-4-induced CD23 expression and release. In addition to these phenotypical changes, IL-4 primed the phorbol-12-myristate-13-acetate (PMA)-induced luminol-dependent chemiluminescence response (LDCL) by normal human monocytes; this priming effect was abrogated in the presence of Lyprinol, or of BW B70C. Monocyte-derived monocytes from allergic patients spontaneously produced high amounts of LTB4, expressed CD23 expression, and had an increased oxidative metabolism. In the presence of Lyprinol, or of BW B70C, the hyper-activation of monocytes from allergic patients was significantly suppressed. Taken together, these data indicated that the pharmacological control of the 5-lipoxygenase pathway in human monocytes can be achieved with Lyprinol, and that the activation of this pathway could upregulate the expression and release of CD23 and the respiratory burst of human monocytes.
authors.affiliation: Oxykine Therapeutics S.A., Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Dugas
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D049872:Bivalvia / Q000737:chemistry*; D002478:Cells, Cultured; D003864:Depression, Chemical; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000096:biosynthesis* / Q000235:genetics; D008055:Lipids / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009520:New Zealand; D017455:Receptors, IgE / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008055:Lipids; D016859:Lipoxygenase Inhibitors; D017455:Receptors, IgE; D011994:Recombinant Proteins; C418997:lyprinol; C080871:BW B70C; D007975:Leukotriene B4; D015847:Interleukin-4; D001094:Arachidonate 5-Lipoxygenase; D013755:Tetradecanoylphorbol Acetate; D006918:Hydroxyurea