IL-4 inhibits calcium transients in bovine trachealis cells by a ryanodine receptor dependent mechanism

Article

关键词: AIRWAY SMOOTH-MUSCLE;    CYCLIC-ADP-RIBOSE;    CYCLOPIAZONIC ACID;    EOTAXIN RELEASE;    CYTOSOLIC CA2+;    INTERLEUKIN-4;    CHANNEL;    MODULATION;    EXPRESSION;    CYTOKINES;   

DOI  :  10.1096/fj.05-4031fje

来源: SCIE

【 摘 要 】

IL-4 and IL-13 have important roles in the pathogenesis of asthma. A novel finding was that brief exposure of airway smooth muscle cells to IL-4 inhibited carbachol-stimulated calcium transients. We hypothesized that IL-4 inhibits transients by decreasing calcium store content and tested this by measuring the effects of IL-4 on transients induced by a nonspecific ionophore. Bovine trachealis cells were loaded with fura 2-AM, and cytosolic calcium concentrations ([Ca2+]i) were measured in single cells by digital microscopy. Stimulation (S1) with carbachol (10 mu M) caused rapid, transient increases in [Ca2+](i) to 1299 +/- 355 nM (n= 5). After recovery of calcium stores, stimulation (S2) of the same cells with ionomycin (10 mu M), in the absence of extracellular calcium, also increased [Ca2+](i) to give S2/S1 ratio of 1.03 +/- 0.29. However, after 20 min of IL-4 (50 ng/ml), but not IL-13, ionomycin transients were decreased to 0.50 +/- 0.16 (S2/S1, P=0.02, n= 6). IL-4 did not inhibit transients with ryanodine receptor calcium release channels (RyR) blocked by ryanodine (200 mu M) (S2/S1= 1.01 +/- 0.11) but still did in the presence of 8-bromo cyclic ADP-ribose, an antagonist of cyclic ADP-ribose (cADPR) signaling at RyR (S2/S1= 0.48 +/- 0.13). Together, findings suggest that IL-4 decreases intracellular calcium stores by mechanisms dependent on RyR, but not on cADPR signaling.

【 授权许可】

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