Nonmuscle myosin light chain kinase regulates murine asthmatic inflammation Article

Wang, T, Moreno-Vinasco, L, Ma, SF et al. (2014). Nonmuscle myosin light chain kinase regulates murine asthmatic inflammation . AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 50(6), 1129-1135. 10.1165/rcmb.2013-0434OC

cited authors

  • Wang, T; Moreno-Vinasco, L; Ma, SF; Zhou, T; Shimizu, Y; Sammani, S; Epshtein, Y; Watterson, DM; Dudek, SM; Garcia, JGN

authors

abstract

  • Myosin light chain kinase (MLCK; gene code, MYLK) is a multifunctional enzyme involved in isoform-specific nonmuscle (nm) and smooth muscle contraction, inflammation, and vascular permeability, processes directly relevant to asthma pathobiology. In this report, we highlight the contribution of the nm isoform (nmMLCK) to asthma susceptibility and severity, supported by studies in two lines of transgenic mice with knocking out nmMLCK or selectively overexpressing nmMLCK in endothelium. These mice were sensitized to exhibit ovalbumin-mediated allergic inflammation. Genetically engineered mice with targeted nmMLCK deletion (nmMLCK-/-) exhibited significant reductions in lung inflammation and airway hyperresponsiveness. Conversely, mice with overexpressed nmMLCK in endothelium (nmMLCKec/ec) exhibited elevated susceptibility and severity in asthmatic inflammation. In addition, reduction of nmMLCK expression in pulmonary endothelium by small interfering RNA results in reduced asthmatic inflammation in wild-type mice. These pathophysiological assessments demonstrate the positive contribution of nmMLCK to asthmatic inflammation, and a clear correlation of the level of nmMLCK with the degree of experimental allergic inflammation. This study confirms MYLK as an asthma candidate gene, and verifies nmMLCK as a novel molecular target in asthmatic pathobiology. Copyright © 2014 by the American Thoracic Society.

publication date

  • January 1, 2014

published in

Digital Object Identifier (DOI)

start page

  • 1129

end page

  • 1135

volume

  • 50

issue

  • 6