Hyperosmolarity-induced interleukin-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase

Am J Respir Crit Care Med. 1999 Feb;159(2):634-40. doi: 10.1164/ajrccm.159.2.9712090.


The changes in airway osmolarity have been described to contribute to the production of exercise- induced bronchoconstriction (EIB) and the development of the late-phase response (LPR). The mechanism has been investigated; however, the responsiveness of bronchial epithelial cells (BEC) to hyperosmolarity and the intracellular signals leading to cell activation have not been determined. In this study, we examined the effect of hyperosmolar medium on interleukin-8 (IL-8) expression and the role of p38 mitogen-activated protein (MAP) kinase and c-Jun NH2 terminal kinase ( JNK) in human BEC in this response in order to clarify the intracellular signals regulating IL-8 expression in hyperosmolarity-stimulated BEC. The results showed that hyperosmolarity induced IL-8 expression in a concentration dependent manner, p38 MAP kinase phosphorylation and activation, and JNK activation whether NaCl or mannitol was used as the solute. SB 203580 as the specific p38 MAP kinase inhibitor inhibited hyperosmolarity-induced p38 MAP kinase activation and partially inhibited hyperosmolarity-induced IL-8 expression. These results indicate that p38 MAP kinase, at least in part, regulates hyperosmolarity-induced IL-8 expression in BEC. However, other signals such as JNK are possibly also involved. These results provide new evidence on the mechanism responsible for the development of the LPR induced by EIB, and a strategy for treatment with the specific p38 MAP kinase inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • Blotting, Northern
  • Blotting, Western
  • Bronchi / cytology
  • Bronchi / metabolism*
  • Bronchial Hyperreactivity / drug therapy
  • Bronchial Hyperreactivity / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / metabolism*
  • Gene Expression
  • Humans
  • Imidazoles / pharmacology
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Mannitol / pharmacology
  • Mitogen-Activated Protein Kinases*
  • Osmolar Concentration
  • Phosphorylation / drug effects
  • Pyridines / pharmacology
  • RNA, Messenger / metabolism
  • Saline Solution, Hypertonic / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Tyrosine / metabolism
  • p38 Mitogen-Activated Protein Kinases


  • Enzyme Inhibitors
  • Imidazoles
  • Interleukin-8
  • Pyridines
  • RNA, Messenger
  • Saline Solution, Hypertonic
  • Mannitol
  • Tyrosine
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580