Background: Activated inflammatory cells are found in coronary plaques as well as peripheral circulation in patients with acute coronary syndrome. We explored the circulating T cell profile, their reactivity to self-a...Background: Activated inflammatory cells are found in coronary plaques as well as peripheral circulation in patients with acute coronary syndrome. We explored the circulating T cell profile, their reactivity to self-antigens and plasma cytokine levels in Indian patients with Myocardial Infarction. Methods and Results: Intracellular expression of interferon-γ Interleukin (IL)-4, IL-17, IL-10 and Foxp3 were determined in CD4+ and CD8+ T cells using flow cytometry in patients with ST elevated myocardial infarction (STEMI) (N = 79) and controls (N = 80). Cytokines were measured using Milliplex kit and T cell reactivity was studied by CFSE dilution. Statistical analysis was performed using SPSS software. Patients with myocardial infarction showed higher proportion of IL-17 expressing CD4+ and CD8+ T cells (Th17 and Tc17) and elevated levels of IL-6 and IL-17 in plasma with significant reduction in circulating Tregs. Th1, Th2 and CD4+CD28null cells were not significantly different in patients compared to healthy individuals. The ratio of Th17 and Tc17 to Tregs showed an independent association with STEMI with an adjusted odds ratio of 2.92 (95% CI: 1.73 - 4.92), P + and CD8+ T cells secreting IL-17 and Tregs is associated with acute myocardial infarction. HSP60 and Ox-LDL may contribute to this response and pathogenesis of AMI in Indian population.展开更多
We have investigated the earliest events in commitment of human epidermal keratinocytes to terminal differentiation. Phosphorylated Akt and caspase activation were detected in cells exiting the basal layer of the epid...We have investigated the earliest events in commitment of human epidermal keratinocytes to terminal differentiation. Phosphorylated Akt and caspase activation were detected in cells exiting the basal layer of the epidermis. Activation of Akt by retroviral transduction of primary cultures of human keratinocytes resulted in an increase in abortive clones founded by transit amplifying cells, while inhibition of the upstream kinase, PI3-kinase, inhibited suspension-induced terminal differentiation. Caspase inhibition also blocked differentiation, the primary mediator being caspase 8. Caspase activation was initiated by 2 h in suspension, preceding the onset of expression of the termi- nal differentiation marker involucrin by several hours. Incubation of suspended cells with fibronectin or inhibition of PI3-kinase prevented caspase induction. At 2 h in suspension, keratinocytes that had become committed to terminal differentiation had increased side scatter, were 7-aminoactinomycin D （7-AAD） positive and annexin V negative; they exhibited loss of mitochondrial membrane potential and increased cardiolipin oxidation, but with no increase in reac- tive oxygen species. These properties indicate that the onset of terminal differentiation, while regulated by PI3-kinase and caspases, is not a classical apoptotic process.展开更多
文摘Background: Activated inflammatory cells are found in coronary plaques as well as peripheral circulation in patients with acute coronary syndrome. We explored the circulating T cell profile, their reactivity to self-antigens and plasma cytokine levels in Indian patients with Myocardial Infarction. Methods and Results: Intracellular expression of interferon-γ Interleukin (IL)-4, IL-17, IL-10 and Foxp3 were determined in CD4+ and CD8+ T cells using flow cytometry in patients with ST elevated myocardial infarction (STEMI) (N = 79) and controls (N = 80). Cytokines were measured using Milliplex kit and T cell reactivity was studied by CFSE dilution. Statistical analysis was performed using SPSS software. Patients with myocardial infarction showed higher proportion of IL-17 expressing CD4+ and CD8+ T cells (Th17 and Tc17) and elevated levels of IL-6 and IL-17 in plasma with significant reduction in circulating Tregs. Th1, Th2 and CD4+CD28null cells were not significantly different in patients compared to healthy individuals. The ratio of Th17 and Tc17 to Tregs showed an independent association with STEMI with an adjusted odds ratio of 2.92 (95% CI: 1.73 - 4.92), P + and CD8+ T cells secreting IL-17 and Tregs is associated with acute myocardial infarction. HSP60 and Ox-LDL may contribute to this response and pathogenesis of AMI in Indian population.
文摘We have investigated the earliest events in commitment of human epidermal keratinocytes to terminal differentiation. Phosphorylated Akt and caspase activation were detected in cells exiting the basal layer of the epidermis. Activation of Akt by retroviral transduction of primary cultures of human keratinocytes resulted in an increase in abortive clones founded by transit amplifying cells, while inhibition of the upstream kinase, PI3-kinase, inhibited suspension-induced terminal differentiation. Caspase inhibition also blocked differentiation, the primary mediator being caspase 8. Caspase activation was initiated by 2 h in suspension, preceding the onset of expression of the termi- nal differentiation marker involucrin by several hours. Incubation of suspended cells with fibronectin or inhibition of PI3-kinase prevented caspase induction. At 2 h in suspension, keratinocytes that had become committed to terminal differentiation had increased side scatter, were 7-aminoactinomycin D （7-AAD） positive and annexin V negative; they exhibited loss of mitochondrial membrane potential and increased cardiolipin oxidation, but with no increase in reac- tive oxygen species. These properties indicate that the onset of terminal differentiation, while regulated by PI3-kinase and caspases, is not a classical apoptotic process.
