Abstract | BACKGROUND:
Minocycline exhibits anti-inflammatory properties independent of its antibiotic activity, ameliorating inflammatory responses in monocytes and macrophages. However, the mechanisms of minocycline anti-inflammatory effects are only partially understood. METHODS: Human circulating monocytes were cultured in the presence of lipopolysaccharide (LPS), 50 ng/ml, and minocycline (10-40 μM). Gene expression was determined by RT-PCR, cytokine and prostaglandin E(2) ( PGE(2)) release by ELISA, protein expression, phosphorylation and nuclear translocation by Western blotting. RESULTS: CONCLUSIONS: We provide novel evidence demonstrating that the anti-inflammatory effects of minocycline in human monocytes include, in addition to decreased NF-κB activation, abrogation of the LPS-stimulated LOX-1, LITAF, Nur77 pathways, p38 MAPK inhibition and PI3K/Akt activation. Our results reveal that minocycline inhibits points of convergence of distinct and interacting signaling pathways mediating multiple inflammatory signals which may influence monocyte activation, traffic and recruitment into the brain. GENERAL SIGNIFICANCE: Our results in primary human monocytes contribute to explain the profound anti-inflammatory and protective effects of minocycline in cardiovascular and neurological diseases and may have direct translational relevance.
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Authors | Tao Pang, Juan Wang, Julius Benicky, Juan M Saavedra |
Journal | Biochimica et biophysica acta
(Biochim Biophys Acta)
Vol. 1820
Issue 4
Pg. 503-10
(Apr 2012)
ISSN: 0006-3002 [Print] Netherlands |
PMID | 22306153
(Publication Type: Journal Article, Research Support, N.I.H., Intramural)
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Copyright | Published by Elsevier B.V. |
Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Interleukin-1beta
- Interleukin-6
- LITAF protein, human
- Lipopolysaccharides
- NF-kappa B
- NR4A1 protein, human
- Nuclear Proteins
- Nuclear Receptor Subfamily 4, Group A, Member 1
- OLR1 protein, human
- Scavenger Receptors, Class E
- Transcription Factors
- Tumor Necrosis Factor-alpha
- Cyclooxygenase 2
- Phosphatidylinositol 3-Kinases
- Proto-Oncogene Proteins c-akt
- p38 Mitogen-Activated Protein Kinases
- Minocycline
- Dinoprostone
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Topics |
- Active Transport, Cell Nucleus
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology)
- Cells, Cultured
- Cyclooxygenase 2
(genetics)
- Dinoprostone
(biosynthesis)
- Humans
- Inflammation
(drug therapy)
- Interleukin-1beta
(genetics)
- Interleukin-6
(genetics, metabolism)
- Lipopolysaccharides
(immunology)
- Macrophages
(drug effects, immunology)
- Minocycline
(pharmacology)
- Monocytes
(drug effects, immunology, microbiology)
- NF-kappa B
(antagonists & inhibitors)
- Nuclear Proteins
(antagonists & inhibitors)
- Nuclear Receptor Subfamily 4, Group A, Member 1
(antagonists & inhibitors)
- Phosphatidylinositol 3-Kinases
(biosynthesis)
- Phosphorylation
- Proto-Oncogene Proteins c-akt
(biosynthesis)
- Scavenger Receptors, Class E
(antagonists & inhibitors)
- Signal Transduction
(drug effects, immunology)
- Transcription Factors
(antagonists & inhibitors)
- Transcription, Genetic
(drug effects)
- Tumor Necrosis Factor-alpha
(genetics, metabolism)
- p38 Mitogen-Activated Protein Kinases
(biosynthesis)
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