Proteomic analysis of the anti-inflammatory action of minocycline

Christopher R Dunston, Helen R Griffiths, Peter A Lambert, Susan Staddon, Ann B Vernallis

Research output: Contribution to journalArticle

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.
LanguageEnglish
Pages42-51
Number of pages10
JournalProteomics
Volume11
Issue number1
Early online date6 Dec 2010
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Minocycline
Proteomics
Anti-Inflammatory Agents
Lipopolysaccharides
Macrophages
Tetracycline
Nitric Oxide
Aldehyde Reductase
Oxytetracycline
Macrophage Activation
Doxycycline
Proteome
Heat-Shock Proteins
Metabolism
Proteins
Adenosine Triphosphate
Chemical activation
Cytokines
Anti-Bacterial Agents

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

Cite this

Dunston, Christopher R ; Griffiths, Helen R ; Lambert, Peter A ; Staddon, Susan ; Vernallis, Ann B. / Proteomic analysis of the anti-inflammatory action of minocycline. In: Proteomics. 2011 ; Vol. 11, No. 1. pp. 42-51.
@article{2629363a5bb549bdbb5bcaac617604ef,
title = "Proteomic analysis of the anti-inflammatory action of minocycline",
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.",
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",
author = "Dunston, {Christopher R} and Griffiths, {Helen R} and Lambert, {Peter A} and Susan Staddon and Vernallis, {Ann B}",
note = "Copyright {\circledC} 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2011",
month = "1",
doi = "10.1002/pmic.201000273",
language = "English",
volume = "11",
pages = "42--51",
journal = "Proteomics",
issn = "1615-9853",
publisher = "Wiley-VCH Verlag",
number = "1",

}

Proteomic analysis of the anti-inflammatory action of minocycline. / Dunston, Christopher R; Griffiths, Helen R; Lambert, Peter A; Staddon, Susan; Vernallis, Ann B.

In: Proteomics, Vol. 11, No. 1, 01.2011, p. 42-51.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Proteomic analysis of the anti-inflammatory action of minocycline

AU - Dunston, Christopher R

AU - Griffiths, Helen R

AU - Lambert, Peter A

AU - Staddon, Susan

AU - Vernallis, Ann B

N1 - Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PY - 2011/1

Y1 - 2011/1

N2 - 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.

AB - 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.

KW - animals

KW - anti-inflammatory agents

KW - cell line

KW - liquid chromatography

KW - two-dimensional electrophoresis

KW - immunoblotting

KW - lLipopolysaccharides

KW - mass spectrometry

KW - mice

KW - minocycline

KW - nitric oxide

KW - nitric oxide synthase type II

KW - proteomics

KW - tetracyclines

UR - http://www.scopus.com/inward/record.url?scp=78650408816&partnerID=8YFLogxK

UR - http://onlinelibrary.wiley.com/doi/10.1002/pmic.201000273/abstract

U2 - 10.1002/pmic.201000273

DO - 10.1002/pmic.201000273

M3 - Article

VL - 11

SP - 42

EP - 51

JO - Proteomics

T2 - Proteomics

JF - Proteomics

SN - 1615-9853

IS - 1

ER -