Open AccessInteraction between Cl − channels and CRAC‐related Ca 2+ signaling during T lymphocyte activation and proliferation 1
Author(s) -
WANG Guanlei,
QIAN Yan,
QIU Qinying,
LAN Xiujian,
HE Hua,
GUAN Yongyuan
Publication year - 2006
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2006.00297.x
Subject(s) - lymphocyte activation , signal transduction , t lymphocyte , chemistry , microbiology and biotechnology , immunology , biology , biochemistry , t cell , immune system
Aim: To test the hypothesis that Cl − 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 Cl − channel blocker on concanavalin A (ConA; 5 mg/mL)‐induced Ca 2+ signaling, gene expression and cellular proliferation in human peripheral T lymphocytes. Methods: [ 3 H]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 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}‐1 H ‐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%, whereasDIDS(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.