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Interplay of pro‐inflammatory and anti‐inflammatory cytokines in regulating oxidative stress in isolated adult rat cardiac myocytes
Author(s) -
Kaur Kuljeet,
Sharma Anita K.,
Singal Pawan K
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1451-b
Subject(s) - oxidative stress , superoxide dismutase , lipid peroxidation , proinflammatory cytokine , glutathione peroxidase , chemistry , catalase , tumor necrosis factor alpha , endocrinology , cytokine , antioxidant , medicine , inflammation , biochemistry , biology
Interleukin‐10 (IL‐10), an anti‐inflammatory cytokine, has been shown to antagonize some of deleterious effects of pro‐inflammatory cytokine, Tumor Necrosis Factor‐α (TNF‐α). We hypothesized that the balance between TNF‐α and IL‐10 is of greater significance in regulating oxidative stress. Methods Myocytes were exposed for 4 hours to different doses of IL‐10 (1–20 ng/ml) or combination of TNF‐α and IL‐10 in different ratios. Cell lysates were analyzed for protein levels and mRNA levels for Copper/zinc superoxide dismutase [CuSOD], Manganese superoxide dismutase [MnSOD], Catalase [Cat] and Glutathione peroxidase [GSHPx]. Oxidative stress was assessed by redox‐sensitive fluorescence dye (H2DCFDA) as well as by the study of lipid peroxidation. Effects of oxidative stress induced by H 2 O 2 on these parameters were also examined for comparison purposes. Results H 2 O 2 treatment significantly decreased protein and mRNA levels of all four antioxidants. IL‐10 treatment alone had no effect on the protein levels of antioxidants but caused a dose dependent increase in the mRNA levels of all antioxidant enzymes with a significant change seen at 20 ng/ml. TNF‐α induced decrease in MnSOD, Cat and GSHPx protein levels were prevented by IL‐10/TNF‐α ratio of 1. Similarly this ratio of 1 had an optimal effect on the mRNA levels for MnSOD and Cat. Combination treatment at a ratio of 1 also significantly decreased lipid peroxidation and intracellular ROS. Conclusion This study suggests that the relative concentration of TNF‐α and IL‐10 is of more physiological importance than either of the cytokines individually. Supported by ICRH