Tumor necrosis factor-α inhibits effects of aryl hydrocarbon receptor ligands on cell death in human lymphocytes


1 Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan; Department of Stem Cell Biology, Stem Cell Technology Research Center, Tehran, Iran

2 Department of Hematology, Tarbiat Modares University, Tehran, Iran

3 Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

5 Department of Stem Cell Biology, Stem Cell Technology Research Center; Department of Hematology, Tarbiat Modares University, Tehran, Iran


Background: Activation of aryl hydrocarbon receptor (AhR) leads to diverse outcome in various kinds of cells. AhR activation may induce apoptosis or prevent of apoptosis and cell death. Recent studies suggest that apoptosis effects of AhR can be modulated by inflammatory cytokine like tumor necrosis factor alpha (TNF-α). In this study, we try to investigate the possible interaction of TNF-α with the 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD), a ligand of AhR, on peripheral lymphocytes.
Materials and Methods: Human peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood by discontinuous density gradient centrifugation on ficoll. Isolated PBMCs were divided into four groups: Control group, TNF-α administered group, TCDD administered group, co-administered group with TCDD and TNF-α. Cells were maintained for a week in lymphocyte culture condition. Then, TNF-α was added to group 2 and 4. Finally, apoptosis and necrosis were analyzed in all samples using flowcytometry.
Result: In group 4, the mean percent of necrosis and apoptosis in TCDD treatment groups was significantly larger than other groups; (P < 0.05). Furthermore, there was no significant difference between the mean percent of cell death in TNF-α administered group and TCDD administered group (P > 0.05). However, the mean percent of cell death in co-administered group with TCDD and TNF-α was significantly lower than other groups; (P < 0.05).
Conclusion: TNF-α could significantly inhibit effects of TCDD on lymphocytes apoptosis. Combination effects of TNF-α and TCDD on lymphocyte increase cell survival.


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