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

Ethier, Michael F.; Madison, J. Mark

doi:10.1096/fj.05-4031fje

Cited by 10 publications

(12 citation statements)

References 40 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…release of Ca 2+ through RyR leads to activation of K + channels, membrane hyperpolarisation and closure of voltage-dependent Ca 2+ channels. In the present study, isoproterenol did appear to promote Ca 2+ release through RyR (figs 6 and 7); this was also documented using the nitric oxide donor SNAP [32], and the same response was found upon stimulation with isoproterenol [13] and interleukin-4 [12]. Nonetheless, contraction of ASM is normally poorly dependent upon electromechanical coupling and, in the present study, the bronchodilatory action of isoproterenol was found to be largely unaffected by inhibition of RyR.…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

Ryanodine receptors decant internal Ca2+ store in human and bovine airway smooth muscle

Tazzeo¹,

Zhang²,

Keshavjee³

et al. 2008

European Respiratory Journal

View full text Add to dashboard Cite

Several putative roles for ryanodine receptors (RyR) were investigated in human and bovine airway smooth muscle.Changes in intracellular Ca 2+ concentration ([Ca 2+ ] i ) and membrane current were investigated in single cells by confocal fluorimetry and patch-clamp electrophysiology, respectively, whereas mechanical activity was monitored in intact strips with force transducers.RyR released Ca 2+ from the sarcoplasmic reticulum in a ryanodine-and chloroethyl phenol (CEP)-sensitive fashion. Neither ryanodine nor CEP inhibited responses to KCl, cholinergic agonists or serotonin, indicating no direct role for RyR in contraction; in fact, there was some augmentation of these responses. In tissues pre-contracted with carbachol, the concentrationresponse relationships for isoproterenol and salmeterol were unaffected by ryanodine; relaxations due to a nitric oxide donor were also largely unaffected. Finally, it was examined whether RyR were involved in regulating [Ca 2+ ] i within the subplasmalemmal space using patchclamp electrophysiology as well as Ca 2+ fluorimetry: isoproterenol increased [Ca 2+ ] i -and Ca 2+ -dependent K + current activity in a ryanodine-sensitive fashion.In conclusion, ryanodine receptors in airway smooth muscle are not important in directly mediating contraction or relaxation. The current authors speculate instead that these allow the sarcoplasmic reticulum to release Ca 2+ towards the plasmalemma (to unload an overly full Ca 2+ store and/or increase the Ca 2+-buffering capacity of the sarcoplasmic reticulum) without affecting bronchomotor tone.

show abstract

Section: Discussionsupporting

confidence: 83%

“…The role of RyR in ASM in particular is still not entirely clear, with some proposing its importance in bronchoconstriction [3,[6][7][8][9][10][11] or in bronchodilation [12,13], and others finding no detectable role [14]. In the present study, the role of RyR in human and bovine ASM was investigated using Ca…”

Section: +mentioning

confidence: 94%

Ryanodine receptors decant internal Ca2+ store in human and bovine airway smooth muscle

Tazzeo¹,

Zhang²,

Keshavjee³

et al. 2008

European Respiratory Journal

View full text Add to dashboard Cite

show abstract

“…The IL-4 concentrations used during this study were similar to those employed in previous in vitro studies (10-50 ng/ml). 61,62 In a model of IL-4-induced rat hepatitis, IL-4 serum concentrations reached 1800 pg/ml. 63 In HIV-Trypanosoma cruzi coinfection, IL-4 serum levels reached 6200 pg/ml.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

Aoudjehane

Pissaia

Scatton

et al. 2008

Laboratory Investigation

View full text Add to dashboard Cite

Interleukin-4 (IL-4) is overexpressed in liver grafts in a context of severe recurrent hepatitis C, during which the development of fibrosis is dramatically accelerated. In this study, we examined the effects of IL-4 on the activation and collagen production of cultured human intrahepatic (myo)fibroblasts (hIHFs), and investigated the underlying mechanisms. The myofibroblastic nature of cells was evaluated morphologically using activation markers (smooth muscle a-actin, vimentin and prolyl 4-hydroxylase). Quiescent hIHFs were obtained by cell incubation in serum-free medium or cell culture on Matrigel. We first analyzed IL-4 receptor expression, STAT-6 activation by IL-4, and STAT-6 inhibition by an anti-IL-4 antibody or by STAT-6 small-interfering RNA (siRNA) transfection. We then focused on collagen production, using quantitative real-time PCR to analyze the effect of IL-4 on the mRNA expression of collagens I, III and IV, and on collagen levels in supernatants of hIHFs, using the Sircol collagen assay. hIHFs cultured in plastic wells appeared to be morphologically activated. The expression of activation markers was reduced by serum deprivation or culture on Matrigel, and restored by IL-4 incubation. The IL-4 receptor was expressed by hIHFs, and STAT-6 was activated following incubation with IL-4. Both anti-IL-4 antibody and STAT-6 siRNA transfection inhibited this activation. The treatment of hIHFs with IL-4 increased the mRNA expression of collagens I, III and IV (Po0.05) and elevated collagen levels in supernatants (P ¼ 0.01 vs untreated cells). Therefore, IL-4 exerts profibrotic effects by activating hIHFs and inducing collagen production and secretion. This effect requires IL4-R binding and STAT-6 activation. IL-4 may thus be involved in accelerated course of fibrogenesis during recurrent hepatitis C.

show abstract

“…The IL‐4 concentrations used here were similar to those used in previous in vitro studies (50 ng/ml; refs. 27, 51), although no information is available on IL‐4 concentrations in liver or serum after liver transplantation. In a model of rat hepatitis induced by IL‐4, the IL‐4 serum concentration reached 1800 pg/ml (52).…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐4 induces human hepatocyte apoptosis through a Fas‐independent pathway

et al. 2007

View full text Add to dashboard Cite

IL-4 is overexpressed in liver grafts during severe recurrent hepatitis C and rejection. Hepatocyte apoptosis is involved in both these phenomena. We therefore examined the proapoptotic effect of IL-4 on HepG2 cells and human hepatocytes in vitro, together with the underlying mechanisms. We first measured IL-4 receptor expression, STAT6 activation by IL-4, and STAT6 inhibition by an anti-IL-4 antibody or by STAT6 siRNA transfection. We then focused on the pathways involved in IL-4-mediated apoptosis and the role of STAT6 activation in apoptosis initiation. The IL-4 receptor was expressed on both cell types, and STAT6 was activated by IL-4. Both anti-IL-4 and STAT-6 siRNA inhibited this activation. IL-4 induced apoptosis of both HepG2 cells (P=0.008 vs. untreated control) and human hepatocytes (P<0.001 vs. untreated control). IL-4 reduced the mitochondrial membrane potential, activated Bid and Bax, and augmented caspase 3, 8, and 9 activity. STAT6 blockade inhibited IL-4-induced apoptosis. Expression of Fas and Fas ligand was unaffected when HepG2 cells and hepatocytes were cultured with IL-4, and Fas/FasL pathway blockade failed to inhibit IL-4-induced apoptosis. These results show that IL-4 induces apoptosis of human hepatocytes through IL-4 receptor binding, STAT6 activation, decreased mitochondrial membrane potential, and increased caspase activation, independently of the Fas pathway. IL-4 might thus contribute to the progression of severe liver graft damage.

show abstract

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

Cited by 10 publications

References 40 publications

Ryanodine receptors decant internal Ca2+ store in human and bovine airway smooth muscle

Ryanodine receptors decant internal Ca2+ store in human and bovine airway smooth muscle

Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway

Interleukin‐4 induces human hepatocyte apoptosis through a Fas‐independent pathway

Contact Info

Product

Resources

About