Abstract
Aim:
To test the hypothesis that Cl− channel blockers affect T cell proliferation through Ca2+-release-activated Ca2+ (CRAC) signaling and examine the effects of the combination of a CRAC channel blocker and a Cl− channel blocker on concanavalin A (ConA; 5 mg/mL)-induced Ca2+ signaling, gene expression and cellular proliferation in human peripheral T lymphocytes.
Methods:
[3H]Thymidine incorporation, Fura-2 fluorescent probe, RNase protection assay, and reverse transcription-polymerase chain reaction were used.
Results:
The Cl− channel blocker 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS) inhibited ConA-induced Ca2+ influx, interleukin-2 mRNA expression and T lymphocyte proliferation in a concentration-dependent manner, and also enhanced the inhibitory effects of 1-{beta-[3-(4-methoxyphenyl)propoxyl]-4-methoxyphenethyl}-1H-imida-zole (SK&F96365) on the above key events during T cell activation. A combination of DIDS (1 μmol/L) and SK&F96365 (1 μmol/L) significantly diminished ConA-induced ClC-3 mRNA expression by 64%, whereas DIDS(1 μmol/L) or SK&F96365 (1 μmol/L) alone decreased ConA-induced ClC-3 mRNA expression by only 16% and 9%, respectively.
Conclusion:
These results suggest that there is an interaction between CRAC-mediated Ca2+ signaling and DIDS-sensitive Cl− channels during ConA-induced T cell activation and proliferation. Moreover, the DIDS-sensitive Cl− channels may be related to the ClC-3 Cl− channels.
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Project supported by the National Natural Science Foundation of China (No 30271503 and No 30472021), Science Foundation of the Ministry of Education in China and China Medical Board (No 00730).
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Wang, Gl., Qian, Y., Qiu, Qy. et al. Interaction between Cl− channels and CRAC-related Ca2+ signaling during T lymphocyte activation and proliferation. Acta Pharmacol Sin 27, 437–446 (2006). https://doi.org/10.1111/j.1745-7254.2006.00297.x
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DOI: https://doi.org/10.1111/j.1745-7254.2006.00297.x
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