Open Access

ARTICLE

Impact of the anti-inflammatory agent bindarit on the chemokinome: selective inhibition of the monocyte chemotactic proteins

Massimiliano Mirolo^1,*, Marco Fabbri^1,*, Marina Sironi^1,*, Annunciata Vecchi², Angelo Guglielmotti³, Giorgina Mangano³, Giuseppe Biondi³, Massimo Locati^1,4, Alberto Mantovani^1,4

1 Istituto Clinico Humanitas IRCCS, Rozzano, Italy
2 Fondazione Humanitas per la Ricerca, Rozzano, Italy
3 Angelini Research Center, Santa Palomba-Pomezia, Rome, Italy
4 Institute of General Pathology, University of Milan, Milan, Italy

* Corresponding Authors: A. Mantovani, ; M. Locati,

European Cytokine Network 2008, 19(3), 119-122. https://doi.org/10.1684/ecn.2008.0133

Accepted 30 July 2008;

Abstract

Bindarit is an indazolic derivative that is devoid of any immunosuppressive effects and has no effect on arachidonic acid metabolism. However, it has been proved to have anti-inflammatory activity in a number of experimental diseases, including pancreatitis, arthritis, and lupus nephritis. This therapeutic effect has been associated with its ability to interfere selectively with monocyte recruitment, although the underlying molecular mechanisms are unknown. Here we comprehensively examine the effect of bindarit on the chemokine system, and report that in activated monocytes and endothelial cells, it selectively inhibits the production of the monocyte chemotactic protein subfamily of CC inflammatory chemokines (MCP-1/CCL2, MCP-3/CCL7, MCP-2/CCL8). The capacity of bindarit to inhibit the production of a defined set of related CC chemokines by monocytes and endothelial cells likely underlies the anti-inflammatory activity of this agent in disease. The exploitation of the chemokine system as drug target in inflammatory disease has relied mainly on the development of receptor antagonists and blocking antibodies. Here we report on the use of inhibition of synthesis as a potentially viable and selective approach to modify the chemokine system.

---

Keywords

---