Proteomic analysis of the anti-inflammatory action of minocycline

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Abstract

Minocycline possesses anti-inflammatory properties independently of its antibiotic activity although the underlying molecular mechanisms are unclear. Lipopolysaccharide (LPS)-induced cytokines and pro-inflammatory protein expression are reduced by minocycline in cultured macrophages. Here, we tested a range of clinically important tetracycline compounds (oxytetracycline, doxycycline, minocycline and tigecycline) and showed that they all inhibited LPS-induced nitric oxide production. We made the novel finding that tigecycline inhibited LPS-induced nitric oxide production to a greater extent than the other tetracycline compounds tested. To identify potential targets for minocycline, we assessed alterations in the macrophage proteome induced by LPS in the presence or absence of a minocycline pre-treatment using 2-DE and nanoLC-MS. We found a number of proteins, mainly involved in cellular metabolism (ATP synthase ß-subunit and aldose reductase) or stress response (heat shock proteins), which were altered in expression in response to LPS, some of which were restored, at least in part, by minocycline. This is the first study to document proteomic changes induced by minocycline. The observation that minocycline inhibits some, but not all, of the LPS-induced proteomic changes shows that minocycline specifically affects some signalling pathways and does not completely inhibit macrophage activation.

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Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalProteomics
Volume11
Issue number1
Early online date6 Dec 2010
DOIs
Publication statusPublished - Jan 2011

    Keywords

  • animals, anti-inflammatory agents, cell line, liquid chromatography, two-dimensional electrophoresis, immunoblotting, lLipopolysaccharides, mass spectrometry, mice, minocycline, nitric oxide, nitric oxide synthase type II, proteomics, tetracyclines

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