43 research outputs found
Recent Advances and Opportunities in Research on Lupus: Environmental Influences and Mechanisms of Disease
The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis
<p>Abstract</p> <p>Background</p> <p>Many cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8) is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals.</p> <p>Methods</p> <p>Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects). Cells from the 2<sup>nd </sup>to 5<sup>th </sup>passage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca<sup>2+</sup>]<sub>i</sub>), cell contraction, migration and proliferation.</p> <p>Results</p> <p>The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM) induced a peak Ca<sup>2+ </sup>release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p < 0.05). IL-8 induced contraction was greater in CF cells compared to control. Furthermore, IL-8 exposure resulted in greater phosphorylation of myosin light chain (MLC<sub>20</sub>) in CF than in control cells. In addition, MLC<sub>20 </sub>expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells.</p> <p>Conclusion</p> <p>ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC<sub>20</sub>. Higher expression of MLC<sub>20 </sub>by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.</p
Phosphorylation of the Ca2+-pumping ATPase of heart sarcolemma and erythrocyte plasma membrane by the cAMP-dependent protein kinase.
peer reviewedThe Ca2+ ATPase of heart sarcolemma was stimulated by the exposure of sarcolemma vesicles to ATP and the catalytic subunit of the cAMP-dependent protein kinase. The effect of the phosphorylation system was primarily on the Km(Ca2+) of the pumping ATPase. The ATPase purified from heart sarcolemma or erythrocytes became phosphorylated under the conditions mentioned above. Hydroxylamine treatment of the labeled ATPase has shown that the phosphorylation was additive to be acylphosphate formed on the ATPase during the reaction cycle. The stoichiometry of the kinase-promoted phosphorylation (i.e. the fraction of the ATPase molecules that became labeled) approached 30% with both the heart and the erythrocyte enzyme