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Interaction between Cl- channels and CRAC-related Ca2+ signaling during T lymphocyte activation and proliferation

   
@article{APS4048,
	author = {Guan-lei Wang and Yan Qian and Qin-ying Qiu and Xiu-jian Lan and Hua He and Yong-yuan Guan},
	title = {Interaction between Cl- channels and CRAC-related Ca2+ signaling during T lymphocyte activation and proliferation},
	journal = {Acta Pharmacologica Sinica},
	volume = {27},
	number = {4},
	year = {2016},
	keywords = {},
	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 ConAinduced 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-imidazole (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 ConAinduced 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 DIDSsensitive Cl– channels may be related to the ClC-3 Cl– channels.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/4048}
}