The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis
Many cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezingand 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 if constant exposure to inflammatory mediators affects the smooth muscle response to IL-8 in CF patients compared to non-CF individuals.
Methods: Experiments were conducted on cultured ASM cells from subjects with and without CF (control subjects).
Cells from the 2nd to 5th 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 ([Ca2+]i), cell contraction, migration and proliferation.
Results: The IL-8 receptors CXCR1 and CXCR2 were expressed in both control and CF ASM cells to a comparable extent.
IL-8 (100 nM) induced peak Ca2+ release was higher in control than in CF cells: 228.03 +/- 7 nM versus 198.03 +/- 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 (MLC20) in CF than in control cells. In addition, MLC20 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.
Conclusions: ASM cells of CF patients are more contractile to IL-8 than control ASM cells.
This enhanced contractility is due to an increase in the amount of contractile protein MLC20 rather than to an increase in Il-8 sensitivity. Higher expression of MLC20 by CF cells could contribute tothe airway hyperresponsiveness observed in CF patients.
Author: Vasanthi Govindaraju, Marie-Claire Michoud, Pasquale Ferraro, Janine Arkinson, Katherine Safka, Hector Valderrama-Carvajal and James G. Martin
Credits/Source: Respiratory Research 2008, 9:76
Published on: 2008-12-01
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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