Interaction between CI^- channels and CRAC-related Ca^(2+)signaling during T lymphocyte activation and proliferation  

作　　者：Guan-lei WANG Yan QIAN Qin-ying QIU Xiu-jian LAN Hua HE Yong-yuan GUAN 

机构地区：[1]Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou 510089, China

出　　处：《Acta Pharmacologica Sinica》2006年第4期437-446,共10页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(№30271503 and №30472021);Science Foundation of the Ministry of Education in China and China Medical Board(№00730).

摘　　要：Aim： To test the hypothesis that C1^- channel blockers affect T cell proliferation through Ca^2＋-release-activated Ca^2＋ （CRAC） signaling and examine the effects of the combination of a CRAC channel blocker and a C1^- channel blocker on concanavalin A （ConA; 5 mg/mL）-induced Ca^2＋ 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 C1^-channel blocker 4,4^1-diisothiocyanostilbene-2,2^1-disulfonic acid （DIDS） inhibited ConAinduced Ca^2＋ 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 CIC-3 mRNA expression by 64%, whereas DIDS （1 μmol/L） or SK＆F96365 （1 μmol/L） alone decreased ConA-induced CIC-3 mRNA expression by only 16% and 9%, respectively. Conclusion： These results suggest that there is an interaction between CRAC-mediated Ca^2＋ signaling and DIDS-sensitive C1^- channels during ConA-induced T cell activation and proliferation. Moreover, the DIDSsensitive C1^- channels may be related to the CIC-3 C1^- channels.Aim： To test the hypothesis that C1^- channel blockers affect T cell proliferation through Ca^2＋-release-activated Ca^2＋ （CRAC） signaling and examine the effects of the combination of a CRAC channel blocker and a C1^- channel blocker on concanavalin A （ConA; 5 mg/mL）-induced Ca^2＋ 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 C1^-channel blocker 4,4^1-diisothiocyanostilbene-2,2^1-disulfonic acid （DIDS） inhibited ConAinduced Ca^2＋ 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 CIC-3 mRNA expression by 64%, whereas DIDS （1 μmol/L） or SK＆F96365 （1 μmol/L） alone decreased ConA-induced CIC-3 mRNA expression by only 16% and 9%, respectively. Conclusion： These results suggest that there is an interaction between CRAC-mediated Ca^2＋ signaling and DIDS-sensitive C1^- channels during ConA-induced T cell activation and proliferation. Moreover, the DIDSsensitive C1^- channels may be related to the CIC-3 C1^- channels.

关 键 词：T lymphocytes lymphocyte activation chloride channels CALCIUM ion channels INTERLEUKIN-2 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]