Background/aims: It has been suggested that diabetes is associated with immune dysfunction, in which Ca signaling malfunction in lymphocyte may contributes most. However, the pattern of the Ca signal disorder and the mechanism(s) that explains the change are unclear. Here, in this study we aimed to investigate possible changes and mechanism(s) accounting for the internal Ca signals in diabetic T lymphocyte upon stimulation.
Methods And Results: Using Fura-2-AM, we found a significant decrease in Ca influx induced by thapsigargin (TG) and anti-CD3 antibody (OKT3) in T lymphocytes from blood of both diabetes patients and animals. Furthermore, a downregulated Orai1 protein expression, but not mRNA, was also observed in these cells using western blot and qRT-PCR, respectively. In addition, in high-glucose and agonist treated Jurkat T cells, Ca entry and the release of interleukin-2 (IL-2) were also decreased. Orai1 expression reduced, while stromal interaction molecule 1 (STIM1) and other downstream proteins remained unchanged.
Conclusion: This study demonstrates that the declined Orai1 expression, at least partly, contributes to the downregulated Ca entry during lymphocyte excitation, providing an important mechanism for T lymphocyte malfunction in diabetes.
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| http://dx.doi.org/10.1016/j.bbrc.2018.04.083 | DOI Listing |
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