Benzydamine inhibits monocyte migration and MAPK activation induced by chemotactic agonists

Elena Riboldi, Giada Frascaroli, Pietro Transidico, Walter Luini, Sergio Bernasconi, Francesca Mancini, Angelo Guglielmotti, Claudio Milanese, Mario Pinza, Silvano Sozzani, Alberto Mantovani

Research output: Contribution to journalArticle

Abstract

1. The present study was aimed to investigate the effect of benzydamine, an anti-inflammatory drug devoid of activity on arachidonic acid metabolism, on monocyte chemotaxis and to define the possible biochemical correlates of activity. 2. Benzydamine inhibited monocyte chemotaxis in response to three classes of chemoattractants: the prototypic CC-chemokine CCL2 (MCP-1), the microbial product fMLP and the complement cascade component C5a. The effect was dose-dependent with IC 50's of 100, 50 and 45 μM for MCP-1/CCL2, fMLP and C5a, respectively. At the dose of 100 μM, the effect resulted in a 50 ± 10% inhibition of MCP-1/CCL2-induced chemotaxis and 53 ± 6 and 54 ± 5% inhibitions of chemotaxis in response of fMLP and C5a, respectively (n = 3). 3. Receptor expression as well as calcium fluxes in response to chemoattractants were not affected by benzydamine. 4. Benzydamine strongly inhibited chemoattractant-induced activation of the mitogen-activated protein kinase (MAPK) ERK1/2, and of its upstream activator kinase MEK1/2. ERK1/12 activation in response to chemoattractants was 89-98% inhibited by a 100 μM concentration of benzydamine with an IC 50 of 30 μM. 5. Under the same experimental conditions, pretreatment with 100 μM benzydamine caused a 75-89% inhibition of p38 activation (IC 50 25 μM). 6. These results indicate that the anti-inflammatory activity of benzydamine is exerted at multiple levels, including monocyte migration to chemotactic factors associated to a blockage of ERK and p38 MAPK pathways.

Original languageEnglish
Pages (from-to)377-383
Number of pages7
JournalBritish Journal of Pharmacology
Volume140
Issue number2
DOIs
Publication statusPublished - Sep 2003

Keywords

  • Benzydamine
  • Chemotaxis
  • ERK1/2
  • MAPK
  • Monocytes
  • p38 MAPK

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Riboldi, E., Frascaroli, G., Transidico, P., Luini, W., Bernasconi, S., Mancini, F., Guglielmotti, A., Milanese, C., Pinza, M., Sozzani, S., & Mantovani, A. (2003). Benzydamine inhibits monocyte migration and MAPK activation induced by chemotactic agonists. British Journal of Pharmacology, 140(2), 377-383. https://doi.org/10.1038/sj.bjp.0705428