Nonmuscle myosin light chain kinase regulates murine asthmatic inflammation

Ting Wang, Liliana Moreno-Vinasco, Shwu Fan Ma, Tong Zhou, Yuka Shimizu, Saad Sammani, Yulia Epshtein, D. Martin Watterson, Steven M. Dudek, Joe G.N. Garcia

Research output: Contribution to journalArticle

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1129-1135
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume50
Issue number6
DOIs
StatePublished - Jun 2014

Keywords

  • Asthma
  • Endothelial permeability
  • Nonmuscle myosin light chain kinase
  • Transgenic mice

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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