Interaction between C1^- channels and CRAC-related Ca^2＋ signaling during T lymphocyte activation and proliferation

• Published in: Acta pharmacologica Sinica Vol. 27; no. 4; pp. 437 - 446
• Main Author: Guan-lei WANG Yan QIAN Qin-ying QIU Xiu-jian LAN Hua HE Yong-yuan GUAN
• Format: Journal Article
• Language: English
• Published: 2006
• Subjects: T淋巴细胞; 氯化物; 细胞增生; 钙离子通道
• ISSN: 1671-4083; 1745-7254

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.