Epithelial Cells Induce a Cyclo-Oxygenase-1-Dependent Endogenous Reduction in Airway Smooth Muscle Contractile Phenotype

Am J Respir Cell Mol Biol. 2017 Dec;57(6):683-691. doi: 10.1165/rcmb.2016-0427OC.


Airway smooth muscle cells (ASMCs) are phenotypically regulated to exist in either a proliferative or a contractile state. However, the influence of other airway structural cell types on ASMC phenotype is largely unknown. Although epithelial cells are known to drive ASM proliferation, their effects on the contractile phenotype are uncertain. In the current study, we tested the hypothesis that epithelial cells reduce the contractile phenotype of ASMCs. To do so, we measured force production by traction microscopy, gene and protein expression, as well as calcium release by Fura-2 ratiometric imaging. ASMCs incubated with epithelial-derived medium produced less force after histamine stimulation. We observed reduced expression of myocardin, α-smooth muscle actin, and calponin within ASMCs after coculture with epithelial cells. Peak calcium release in response to histamine was diminished, and depended on the synthesis of cyclo-oxygenase-1 products by ASM and on prostaglandin E receptors 2 and 4. Together, these in vitro results demonstrate that epithelial cells have the capacity to coordinately reduce ASM contraction by functional antagonism and by reduction of the expression of certain contractile proteins.

Keywords: airway smooth muscle cells; calcium; coculture; epithelial cells; excitability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / biosynthesis
  • Calcium Signaling*
  • Calcium-Binding Proteins / biosynthesis
  • Cells, Cultured
  • Cyclooxygenase 1 / biosynthesis*
  • Epithelial Cells / cytology
  • Epithelial Cells / enzymology*
  • Gene Expression Regulation
  • Humans
  • Microfilament Proteins / biosynthesis
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / enzymology*
  • Nuclear Proteins / biosynthesis
  • Receptors, Prostaglandin E, EP2 Subtype / biosynthesis
  • Receptors, Prostaglandin E, EP4 Subtype / biosynthesis
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / enzymology*
  • Trans-Activators / biosynthesis


  • Actins
  • Calcium-Binding Proteins
  • Microfilament Proteins
  • Nuclear Proteins
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Trans-Activators
  • calponin
  • myocardin
  • Cyclooxygenase 1
  • PTGS1 protein, human