A small synthetic molecule capable of preferentially inhibiting the production of the CC chemokine monocyte chemotactic protein-1

Marina Sironi, Angelo Guglielmotti, Nadia Polentarutti, Francesca Fioretti, Claudio Milanese, Maria Romano, Claudio Vigini, Isabella Coletta, Silvano Sozzani, Sergio Bernasconi, Annunciata Vecchi, Mario Pinza, Alberto Mantovani

Research output: Contribution to journalArticle

Abstract

Blocking chemokine production or action is a major target for pharmacological intervention in different human diseases. Bindarit (2-methyl-2-[[1-(phenylmethyl)-1H-indazol-3yl]methoxy]propionic acid) dose-dependently inhibited MCP-1 and TNF-α production induced in vitro in monocytes by LPS and Candida albicans. It did not affect the production of the cytokines IL-1, IL-6, or the chemokines IL-8, MIP-1α and RANTES. In the air pouch model in mice, oral treatment reduced monocyte recruitment and local MCP-1 production, induced by carrageenan or IL-1 injection. In NZB/W mice, a model of lupus nephritis, oral treatment prolonged survival and delayed the onset of proteinuria. The results presented here show that bindarit is a preferential inhibitor of the production of MCP-1 in vitro and in vivo and suggest that its beneficial effects in models of joint and kidney inflammation are related to its anti-MCP-1 action. It is therefore possible to selectively and differentially regulate chemokines by targeting their production with small synthetic molecules.

Original languageEnglish
Pages (from-to)437-441
Number of pages5
JournalEuropean Cytokine Network
Volume10
Issue number3
Publication statusPublished - 1999

Keywords

  • Bindarit
  • Chemokine
  • Inflammation
  • Monocytes
  • Nephritis

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

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    Sironi, M., Guglielmotti, A., Polentarutti, N., Fioretti, F., Milanese, C., Romano, M., Vigini, C., Coletta, I., Sozzani, S., Bernasconi, S., Vecchi, A., Pinza, M., & Mantovani, A. (1999). A small synthetic molecule capable of preferentially inhibiting the production of the CC chemokine monocyte chemotactic protein-1. European Cytokine Network, 10(3), 437-441.