Role of MAP kinase activation in interleukin-8 production by human BEAS-2B bronchial epithelial cells submitted to cyclic stretch

Am J Respir Cell Mol Biol. 2002 Jul;27(1):107-14. doi: 10.1165/ajrcmb.27.1.4766.


Overstretching the airways during positive pressure mechanical ventilation or attacks of acute severe asthma is associated with important biologic responses. Interleukin (IL)-8-dependent neutrophil recruitment seems to play a critical role in the process of mechanical stress-induced airway inflammation. Herein, we show that human bronchial epithelial BEAS-2B cells submitted to cyclic stretch in vitro produce IL-8, at both the mRNA and protein levels. This cellular stress "turns on" activator protein (AP)-1 and cyclic AMP (cAMP)-responding elements. The mitogen-activated protein (MAP) kinases (MAPK) p44/42, SAPK/JNK, and p38 were all rapidly activated (phosphorylated) after the initiation of the cyclic strain (5-10 min). The blockade of p38 with the pharmacologic inhibitor SB203580 abrogated IL-8 production by cell stretching, and an inhibitor of the p44/42 pathway, PD98059, partially inhibited the IL-8 response. A nonspecific tyrosine kinase inhibitor, genistein, also blocked the stretch-induced IL-8 production. This suggests that MAPK, and p38 in particular, are proximal and key intracellular signaling molecules mediating cell activation in response to cyclic stretch, a mechanical strain similar to that applied to lung epithelial cells during mechanical ventilation. Pharmacologic inhibition of the p38 pathway holds promise as a new therapeutic avenue in ventilated patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchi / cytology
  • Bronchi / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Humans
  • Imidazoles / pharmacology
  • Interleukin-8 / biosynthesis*
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • Phosphorylation
  • Pyridines / pharmacology
  • RNA, Messenger / biosynthesis
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / enzymology*
  • Respiratory Mucosa / metabolism
  • Stress, Mechanical*


  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Interleukin-8
  • Pyridines
  • RNA, Messenger
  • Mitogen-Activated Protein Kinases
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one