Stress-activated protein kinases mediate cell migration in human airway epithelial cells

Am J Respir Cell Mol Biol. 2005 Apr;32(4):301-10. doi: 10.1165/rcmb.2004-0118OC. Epub 2005 Jan 24.


Airway epithelial cell (AEC) repair immediately after injury requires coordinated cell spreading and migration at the site of injury. Stress-activated protein kinases such as p38 MAPK and c-Jun N-terminal Protein Kinase (JNK) modulate several responses to cell stress and injury, but their role in AEC migration is not clear. We examined migration in confluent 16HBE14o(-) human AEC lines and in primary AEC grown on collagen-IV. Wounds were created by mechanical abrasion and followed to closure using digital microscopy. Inhibitors of either p38 extracellular signal-regulated kinase (ERK)1/2 (PD98059), mitogen-activated protein kinase (MAPK) (SB203580), or JNK (SP600125) could block cell migration substantially. Inhibiting JNK but not p38 MAPK or ERK1/2 blocked extension of cells into the wound region from the original line of injury. Initial migration was associated with phosphorylation of ERK, p38 MAPK, and JNK within 5-15 min. The downstream effector of p38, heat shock protein 27, also was phosphorylated rapidly after injury; phosphorylation could be blocked by prior treatment with SB203580 but not SP600125. The downstream effector of JNK, c-Jun, likewise was phosphorylated rapidly after injury and could be blocked by inhibiting JNK. Our data demonstrate that p38 MAPK, JNK, and ERK1/2 participate in the early stages of AEC migration.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cells, Cultured
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / enzymology
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism*
  • Respiratory System / cytology*
  • Respiratory System / drug effects
  • Respiratory System / enzymology*
  • Respiratory System / injuries
  • Wound Healing / drug effects
  • Wound Healing / physiology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Enzyme Inhibitors
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases