Proinflammatory effects of malondialdehyde in lymphocytes

Journal of Leukocyte Biology

Somasundaram Raghavan¹  Narkunaraja Shanmugam¹  Ganesan Subramaniyam  and² 

[1]Department of Biomedical Science, Bharathidasan University, Tamilnadu, India

[2] Department of Biochemistry, KAP Viswanathan Government Medical College, Tamilnadu, India Department of Biomedical Science, Bharathidasan University, Tamilnadu, India

关键词: lymphocytes;    malondialdehyde;    oxidative stress;    diabetes;    signaling pathways;    cytokines;   

DOI  :  10.1189/jlb.1211617

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown