Interleukin-13 inhibits proliferation and enhances contractility of human airway smooth muscle cells without change in contractile phenotype

Am J Physiol Lung Cell Mol Physiol. 2011 Jun;300(6):L958-66. doi: 10.1152/ajplung.00247.2010. Epub 2011 Apr 1.


IL-13 is an important mediator of allergen-induced airway hyperresponsiveness. This Th2 cytokine, produced by activated T cells, mast cells, and basophils, has been described to mediate a part of its effects independently of inflammation through a direct modulation of the airway smooth muscle (ASM). Previous studies demonstrated that IL-13 induces hyperresponsiveness in vivo and enhances calcium signaling in response to contractile agonists in vitro. We hypothesized that IL-13 drives human ASM cells (ASMC) to a procontractile phenotype. We evaluated ASM phenotype through the ability of the cell to proliferate, to contract, and to express contractile protein in response to IL-13. We found that IL-13 inhibits human ASMC proliferation (expression of Ki67 and bromodeoxyuridine incorporation) in response to serum, increasing the number of cells in G0/G1 phase and decreasing the number of cells in G2/M phases of the cell cycle. IL-13-induced inhibition of proliferation was not dependent on signal transducer and activator of transcription-6 but was IL-13Rα2 receptor dependent and associated with a decrease of Kruppel-like factor 5 expression. In parallel, IL-13 increased calcium signaling and the stiffening of human ASMC in response to 1 μM histamine, whereas the stiffening response to 30 mM KCl was unchanged. However, Western blot analysis showed unchanged levels of calponin, smooth muscle α-actin, vinculin, and myosin. We conclude that IL-13 inhibits proliferation via the IL-13Rα2 receptor and induces hypercontractility of human ASMC without change of the phenotypic markers of contractility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Bronchi / cytology
  • Bronchi / drug effects*
  • Bronchi / metabolism
  • Calcium Signaling / drug effects
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Contractile Proteins / metabolism
  • Histamine / pharmacology
  • Histamine Agonists / pharmacology
  • Humans
  • Interleukin-13 / pharmacology*
  • Interleukin-13 Receptor alpha1 Subunit / genetics
  • Interleukin-13 Receptor alpha1 Subunit / metabolism
  • Microscopy, Atomic Force
  • Muscle Contraction / drug effects*
  • Myocytes, Smooth Muscle / drug effects*
  • Phenotype
  • RNA, Messenger / genetics
  • Respiratory System / drug effects*
  • Respiratory System / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT6 Transcription Factor / genetics
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction


  • Contractile Proteins
  • Histamine Agonists
  • IL13RA1 protein, human
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • RNA, Messenger
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Histamine