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1.  Interleukin-4 rapidly inhibits calcium transients in response to carbachol in bovine airway smooth muscle cells 
To assess interleukin (IL)-4 effects on calcium signaling, bovine airway smooth muscle cells were loaded with fura-2 and cytosolic calcium ([Ca2+]i) was measured in single cells by digital microscopy. Human, recombinant IL-4 (50 ng/ml) caused small increases in [Ca2+]i. For single cells, carbachol-stimulated calcium transients were compared before (S1) and after (S2) exposure to IL-4 or IL-13. When cells were treated with IL-4 (50 ng/ml) for 20 min, the S2/S1 ratio was 0.17±0.04 (n=7) even though IL-4 had been washed from the chamber for 10 min preceding the S2 response. In contrast, controls not treated with IL-4 had S2/S1 of 0.70±0.04 (n=13, p<0.01). Lower concentrations of IL-4 variably decreased transients and IL-13 had no effect. In other experiments, 5 min of IL-4 did not immediately decrease transients but did after a 25 min delay. Goat, anti-human IL-4 antibody abolished the effect of IL-4. IL-4 (50 ng/ml) also inhibited responses to caffeine (S2/S1: 0.30±0.04 and 0.54±0.06 for IL-4-treated vs control). We concluded that IL-4 rapidly inhibited calcium transients. Since caffeine-stimulated transients were inhibited, IL-4 may act, at least in part, by depleting calcium stores. IL-4 inhibition of cholinergic signaling may be important for modulating airway smooth muscle responses during inflammation.
PMCID: PMC2043474  PMID: 11509335
interleukin (IL)-4; interleukin (IL)-13; calcium; carbachol; cholinergic; caffeine; sarcoplasmic reticulum; thapsigargin; airway smooth muscle; bovine

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