Proinflammatory effects of malondialdehyde in lymphocytes
| Autor: | Narkunaraja Shanmugam, Ganesan Subramaniyam, Somasundaram Raghavan |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
T-Lymphocytes
Blotting Western Immunology Inflammation Pharmacology Biology Lymphocyte Activation Real-Time Polymerase Chain Reaction Transfection medicine.disease_cause Jurkat cells Proinflammatory cytokine Lipid peroxidation Jurkat Cells chemistry.chemical_compound Malondialdehyde Diabetes Mellitus medicine Humans Immunology and Allergy chemistry.chemical_classification Reactive oxygen species Reverse Transcriptase Polymerase Chain Reaction Cell Biology chemistry Cytokines medicine.symptom Signal transduction Reactive Oxygen Species Transcriptome Oxidative stress Signal Transduction |
| Zdroj: | Journal of Leukocyte Biology. 92:1055-1067 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.1211617 |
| Popis: | MDA changed cytokine/chemokines mRNA profiles in lymphocytes; increased cytokines expression is via oxidative stress, p38MAPK, and PKC pathways. Diabetes is an inflammatory disease promoted by alterations in immune cell function. Animal study indicates that T cells are important mediators of inflammation in diabetes. Lipid peroxidation by reactive oxygen species leads to the formation of highly reactive malondialdehyde (MDA), and extensive MDA is found in diabetes. However, the biological functions of MDA have not been studied yet. We hypothesized that increased MDA, as in diabetes, can regulate inflammatory cytokines via specific signaling pathways. This could then result in increased lymphocyte activation and skewing a particular inflammatory subset thereby exacerbates diabetes complications. Commercial cytokine antibody and RT2-PCR array profiling were performed with Jurkat T cells grown with or without MDA. Ingenuity pathways analysis (IPA) and pharmacological inhibitors were used for networks and signaling pathway identification, respectively. For validation, real-time PCR, RT-PCR, and Western blots were performed. MDA induced significant increases in 47 key proinflammatory molecules such as IL-25, IL-6, IL-8, ICAM-1, and light mRNA in Jurkat T cells and primary peripheral blood lymphocytes (PBLCs). A significant 2-fold increase in serum MDA also correlated the increased IL-25 and IL-8 mRNA in PBLCs of diabetic patients. Pharmacological inhibitor studies showed that MDA induced its effect via p38MAPK and protein kinase C pathways. Furthermore, IPA uncovered 5 groups of inflammatory networks and placed our candidate genes in canonical IL-6 and NF-κB signaling pathways and also suggested 5 toxic lists and 3 major toxic functions, namely cardiotoxicity, hepatotoxicity, and nephrotoxicity. These new results suggest that MDA can promote lymphocyte activation via induction of inflammatory pathways and networks. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text