Novel action of n-3 polyunsaturated fatty acids: inhibition of arachidonic acid-induced increase in tumor necrosis factor receptor expression on neutrophils and a role for proteases
| Autor: | Antonio Ferrante, James Irvine, Nahid Moghaddami, Maurizio Costabile, Xiu-Hui Gao, Phulwinder K. Grover, Charles S. T. Hii |
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| Přispěvatelé: | Moghaddami, Nahid, Irvine, James, Gao, Xiuhui, Grover, Phulwinder, Costabile, Maurizio, Hii, Charles, Ferrante, Antonio |
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Proteases Docosahexaenoic Acids Neutrophils Immunology TNF Biology In Vitro Techniques fatty acids Receptors Tumor Necrosis Factor chemistry.chemical_compound Rheumatology Cellular Immunology Internal medicine Fatty Acids Omega-3 arachidonic acid medicine Immunology and Allergy Humans Pharmacology (medical) Protein kinase C Protein Kinase C chemistry.chemical_classification Arachidonic Acid Mitogen-Activated Protein Kinase 3 Dose-Response Relationship Drug neutrophil food and beverages Eicosapentaenoic acid Up-Regulation Endocrinology Mechanism of action chemistry Eicosapentaenoic Acid Gene Expression Regulation Docosahexaenoic acid Tumor necrosis factor alpha Arachidonic acid Calcium medicine.symptom Polyunsaturated fatty acid Peptide Hydrolases |
| Zdroj: | Arthritis and rheumatism. 56(3) |
| ISSN: | 0004-3591 |
| Popis: | Objective Neutrophils and tumor necrosis factor (TNF) play important roles in the pathogenesis of rheumatoid arthritis (RA). Modulation of TNF receptors (TNFRs) may contribute to the regulation of tissue damage, and n-6 polyunsaturated fatty acids (PUFAs) such as arachidonic acid (AA) can increase the expression of TNFRI and TNFRII on neutrophils. Because the n-3 PUFAs are antiinflammatory in RA, we examined whether, as a novel mechanism of action, n-3 PUFAs can antagonize the AA-induced increase in TNFR expression. Methods Human neutrophils were treated with PUFAs and examined for changes in surface expression of TNFRs by flow cytometry. Translocation of protein kinase C (PKC) and activation of ERK-1/2 MAPK were determined by Western blotting. Intracellular calcium mobilization was measured in Fura 2–loaded cells by luminescence spectrometry. Results Pretreatment of neutrophils with nanomolar levels of n-3 PUFAs, eicosapentaenoic acid, or docosahexaenoic acid led to a marked inhibition of the AA-induced up-regulation of TNFRs I and II. Such pretreatment, however, did not prevent AA from stimulating the activities of PKC and ERK-1/2, which is required for the actions of AA or its ability to mobilize Ca2+. Nevertheless, treatment with n-3 PUFAs caused the stimulation of serine proteases that could cleave the TNFRs. Conclusion These findings suggest a mechanism by which the n-3 PUFAs inhibit the inflammatory response in RA, by regulating the ability of AA to increase TNFR expression. These results help fill the gaps in our knowledge regarding the mechanisms of action of n-3 PUFAs, thus allowing us to make specific recommendations for the use of n-3 PUFAs in the regulation of inflammatory diseases. |
| Databáze: | OpenAIRE |
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