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Title

Eukaryotic expression of the broad-spectrum chemokine receptor antagonist vMIP-II and its effects on T-cell function in vitro and in vivo

Authors
Rubant, Simone A.
Ludwig, Ralf J.
Pfeffer, Jeannette
Schulze-Johann, Petra
Kaufmann, Roland
Pfeilschifter, Josef M.
Radeke, Heinfried H.
Published in Experimental Dermatology. 2006, vol. 15, no. 8, p. 634-642
Abstract Pro-inflammatory chemokines and their receptors exhibit elementary functions in cell migration and in Th1-driven inflammatory conditions. One therapeutic strategy to prevent accumulation of pro-inflammatory immune cells is the use of specific chemokine receptor antagonists. An interesting and promising candidate in this context is the viral antagonist MIP-II (vMIP-II) that acts on a broad spectrum of chemokine receptors. To study the in vitro and in vivo effects of vMIP-II on pro-inflammatory chemokine receptor function, we further characterized an ovalbumin-specific murine central memory Th1IF12 clone by using RT-PCR, cDNA array and cytometry. Using in vitro chemotaxis assays we show that eukaryotically generated vMIP-II strongly inhibited migration of CCL2- or CCL5-stimulated Th1 IF12 cells. Using intravital microscopy, we observed that CCL5 induced rolling of Th1 cells in the ear vasculature of C57Bl/6 mice. Pre-treatment with vMIP-II significantly reduced CCL5-induced rolling of Th1 cells to basal levels, indicating, that vMIP-II is also active in vivo (proportion of rolling cells: 19.4 +/- 3.8%, 39.8 +/- 2.9% and 26.1 +/- 3.2%). In addition, investigating the anti-inflammatory action of vMIP-II in adoptive transfer of immunity and dinitrofluorobenzene-induced cutaneous hypersensitivity reaction using C57Bl/6 mice, we show a direct inhibitory effect of vMIP-II on the sensitization phase [Delta ear swelling 62 and 37 cm x 10(-3) for controls and vMIP-II treated mice (2.5 mg/kg), respectively] and effector phase (Delta ear swelling 14.8 and 3.6 cm x 10(-3) for controls and vMIP-II treated mice (2.5 mg/kg), respectively) of cutaneous hypersensitivity. These data indicate that vMIP-II is a promising agent to interfere with chronic inflammatory (skin) diseases.
Keywords AnimalsAnti-HIV Agents/*pharmacologyAnti-Inflammatory Agents/pharmacologyChemokines/*pharmacologyChemotaxisDermatitis, ContactHumansLymphocytes/metabolismMaleMiceMice, Inbred C57BLReceptors, Chemokine/*antagonists & inhibitorsRecombinant Proteins/chemistryT-Lymphocytes/drug effects/*immunology
Identifiers
PMID: 16842602
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RUBANT, Simone A. et al. Eukaryotic expression of the broad-spectrum chemokine receptor antagonist vMIP-II and its effects on T-cell function in vitro and in vivo. In: Experimental Dermatology, 2006, vol. 15, n° 8, p. 634-642. https://archive-ouverte.unige.ch/unige:29781

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Deposited on : 2013-09-20

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