Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Banjanac, M; Munić Kos, V; Nujić, K; Vrančić, M; Belamarić, D; Crnković, S; Hlevnjak, M; Eraković Haber, V.
Anti-inflammatory mechanism of action of azithromycin in LPS-stimulated J774A.1 cells.
Pharmacol Res. 2012; 66(4):357-362
Doi: 10.1016/j.phrs.2012.06.011
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Crnkovic Slaven
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- Abstract:
- Azithromycin is a macrolide antibiotic with well-described anti-inflammatory properties which can be attributed, at least partially, to its action on macrophages. We have previously shown, with 18 different macrolide molecules, that IL-6 and PGE₂ inhibition correlates with macrolide accumulation, as well as with their binding to phospholipids in J774A.1 cells. The present study was performed in order to substantiate the hypothesis that biological membranes are a target for macrolide anti-inflammatory activity. By analyzing the effect of azithromycin on overall eicosanoid production, we found that in LPS-stimulated J774A.1 cells, azithromycin, like indomethacin, inhibited the synthesis of all eicosanoids produced downstream of COX. Upstream of COX, azithromycin inhibited arachidonic acid release in the same way as a cPLA₂ inhibitor, while indomethacin had no effect. Further comparison revealed that in LPS-stimulated J774A.1 cells, the cPLA₂ inhibitor showed the same profile of inhibition as azithromycin in inhibiting PGE₂, IL-6, IL-12p40 and arachidonic acid release. Therefore, we propose that the anti-inflammatory activity of azithromycin in this model may be due to interactions with cPLA₂, causing inadequate translocation of the enzyme or disturbing physical interactions with its substrates. Copyright © 2012 Elsevier Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Anti-Bacterial Agents - immunology
- Anti-Bacterial Agents - pharmacology
- Anti-Inflammatory Agents - immunology
- Anti-Inflammatory Agents - pharmacology
- Anti-Inflammatory Agents, Non-Steroidal - immunology
- Anti-Inflammatory Agents, Non-Steroidal - pharmacology
- Arachidonic Acid - immunology
- Azithromycin - immunology
- Azithromycin - pharmacology
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- Dinoprostone - immunology
- Eicosanoids - immunology
- Group IV Phospholipases A2 - antagonists & inhibitors
- Indomethacin - immunology
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- Lipopolysaccharides - immunology
- Macrophages - drug effects
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- Find related publications in this database (Keywords)
- Azithromycin
- Inflammation
- J774A.1 cells
- LPS
- Cytosolic phospholipase A2