IL-4 inhibits calcium transients in bovine trachealis cells by a ryanodine receptor-dependent mechanism
Department of Medicine, Division of Pulmonary, Allergy and Critical Care
Animals; Calcium; Calcium Signaling; Cattle; Cells, Cultured; Cyclic ADP-Ribose; Interleukin-4; Ionomycin; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum; Trachea
Life Sciences | Medicine and Health Sciences
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 microM) 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 microM), 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 microM) (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.
DOI of Published Version
FASEB J. 2006 Jan;20(1):154-6. Epub 2005 Nov 9. Link to article on publisher's site
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Ethier, Michael F. and Madison, John M., "IL-4 inhibits calcium transients in bovine trachealis cells by a ryanodine receptor-dependent mechanism" (2005). Open Access Articles. 563.